Showing papers by "Allan Linneberg published in 2012"

Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis.

Abstract: Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.

Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

Abstract: Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.

The Association Between IGF-I and Insulin Resistance: A general population study in Danish adults

Abstract: OBJECTIVE IGF-I has an almost 50% amino acid sequence homology with insulin and elicits nearly the same hypoglycemic response. Studies showed that low and high IGF-I levels are related to impaired glucose tolerance and to a higher risk of type 2 diabetes. The aim of the current study was to evaluate the association between IGF-I level and insulin resistance in a Danish general population. RESEARCH DESIGN AND METHODS Included were 3,354 adults, aged 19–72 years, from the cross-sectional Health2006 study. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index to estimate insulin resistance. Serum IGF-I levels were determined by an immunoassay and grouped into quintiles (Q1–Q5). Linear or multinomial logistic regression analyses were performed. RESULTS In the study population, 520 subjects (15.5%) had increased HOMA-IR values above 2.5. After adjustment for age, sex, physical activity, and waist-to-height ratio, a U-shaped association between IGF-I and HOMA-IR was found. Low IGF-I (Q1: odds ratio [OR] 1.65 [95% CI 1.16–2.34], P P CONCLUSIONS Low- and high-normal IGF-I levels are both related to insulin resistance. The biological mechanism of this complex phenomenon has to be elucidated in more detail for future risk stratification.

Contact sensitization to common haptens is associated with atopic dermatitis: new insight

Abstract: Summary Background It has been much debated whether atopic dermatitis (AD) is associated with contact sensitization as past findings have been conflicting. A positive association might change our clinical practice. Objectives To investigate the association between AD and contact sensitization taking the likely route of allergen exposure into account. Methods Questionnaire and clinical data from a cross-sectional study performed in a general population in Copenhagen. In total, 3202 adults aged 18–69 years were patch tested, filaggrin genotyped for 2282del4 and R501X and questioned about AD. Results The variable ‘contact sensitization to at least one allergen, but not nickel and thimerosal’ was significantly associated with AD (odds ratio 2·53, 95% confidence interval 1·59–4·04). The higher prevalence of contact sensitization was driven mainly by fragrance chemicals. In a subanalysis in nonpierced women, a positive association was also found for nickel sensitization. Nickel and thimerosal sensitization may introduce bias in data analysis as these allergies often develop following skin piercing where the skin compartments are bypassed. Conclusions We suspect that individuals with self-reported AD from this study mainly had mild disease. However, clinicians should be aware of increased levels of contact sensitization in individuals with AD. Patch testing should therefore be considered at an early point in individuals with a history of AD and active disease. The fundamental relationship between atopic disease and environmental chemical exposure may be of a more complex and intimate nature than previously supposed.

Serum 25(OH)D and Type 2 Diabetes Association in a General Population: A prospective study

Abstract: OBJECTIVE This study aimed to examine vitamin D status as a determinant for development of type 2 diabetes and deterioration of glucose homeostasis. RESEARCH DESIGN AND METHODS A random sample of the general population of Copenhagen, Denmark, was taken as part of the Inter99 study. Included were 6,405 men and women aged 30–65 years at baseline (1999–2001), with 4,296 participating in the follow-up examination 5 years later (2004–2006). Vitamin D was determined at baseline as serum 25-hydroxyvitamin D [25(OH)D]. Diabetes was defined based on an oral glucose tolerance test and a glycosylated hemoglobin (HbA1c) test. Secondary outcomes included continuous markers of glucose homeostasis. RESULTS The risk of incident diabetes associated with a 10 nmol/L increase in 25(OH)D was odds ratio (OR) 0.91 (95% CI 0.84–0.97) in crude analyses. The association became statistically nonsignificant after adjustment for confounders, with an OR per 10 nmol/L of 0.94 (0.86–1.03). Low 25(OH)D status was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis after adjustment for confounders. Fasting and 2-h glucose and insulin as well as the degree of insulin resistance increased significantly more during follow-up among those with low 25(OH)D levels compared with those with higher levels. CONCLUSIONS Low 25(OH)D status was not significantly associated with incident diabetes after adjustment for confounders. However, it was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis, indicating that low vitamin D status could be related to deterioration of glucose homeostasis.

Vitamin D status and changes in cardiovascular risk factors: a prospective study of a general population.

Abstract: Objectives: A low vitamin D level has been associated with increased cardiovascular disease risk but possible mechanisms remain unclear. We investigated the association between vitamin D levels and 5-year changes in blood pressure, lipid profile and incidence of the metabolic syndrome, hypertension and hypercholesterolemia. Methods: A random sample of 6,784 individuals aged 30–60 years from a general population was investigated in the Inter99 study in 1999–2001. Vitamin D (serum 25-hydroxyvitamin D) was measured at baseline by high-performance liquid chromatography, and 4,330 individuals participated at the 5-year follow-up and were included in the present study. Results: The median baseline vitamin D concentration was 48.0 nmol/l. In multivariable linear regression analyses, a 10 nmol/l higher baseline level of vitamin D was associated with a decrease in triglycerides and very low density lipoprotein cholesterol by 0.52 (p = 0.03) and 0.66% (p = 0.005), respectively. In multivariable logistic regression analyses, the odds ratios per 10 nmol/l higher baseline vitamin D level were 0.95 (p Conclusions: An optimal vitamin D status may influence cardiovascular health by changing the lipid profile in a favorable direction and decreasing the incidence of the metabolic syndrome.

Comorbidity in patients with branch retinal vein occlusion: case-control study

Abstract: Objectives To evaluate comorbidity before and after the diagnosis of branch retinal vein occlusion to determine whether it is a consequence of arterial thickening and therefore could serve as a diagnostic marker for other comorbidities and to evaluate the risk factors for the development of such occlusion.

Association of subcutaneous allergen-specific immunotherapy with incidence of autoimmune disease, ischemic heart disease, and mortality

Abstract: Background Subcutaneous allergen-specific immunotherapy (SCIT) is a well-documented treatment of IgE-mediated allergic disease. Little is known about potential effects of SCIT on the risk of other chronic immune-related diseases. Over the years, a few casuistic reports have caused concern that SCIT might act as a trigger of autoimmune disease. Objective We aimed to investigate the association of SCIT with the incidence of autoimmune disease and ischemic heart disease (IHD), as well as all-cause mortality. Methods All Danish citizens without other known diseases were linked and followed through central registries on medications and hospital admissions. Persons receiving SCIT and persons receiving conventional allergy treatment (CAT; nasal steroids or oral antihistamines) were compared with regard to mortality and development of autoimmune diseases, acute myocardial infarction (AMI), and IHD. Cox regression (survival analysis) with age as the underlying time scale was used to estimate relative risks (hazard ratios [HRs] with 95% CIs) associated with SCIT compared with CAT adjusted for age, sex, vocational status, and income. Results During the 10-year study period (1997-2006), a total of 18,841 and 428,484 persons were followed in the SCIT and CAT groups, respectively. Receiving SCIT was associated with lower mortality (HR, 0.71; 95% CI, 0.62-0.81) and lower incidence of AMI (HR, 0.70; 95% CI, 0.52-0.93), IHD (HR, 0.88; 95% CI, 0.73-1.05), and autoimmune disease (HR, 0.86; 95% CI, 0.74-0.99). Conclusion In this registry-based observational study, receiving SCIT compared with CAT was associated with lower risk of autoimmune disease and AMI, as well as decreased all-cause mortality.

Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis.

Abstract: Diabet. Med. 29, e354–e360 (2012) Abstract Aims Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. Methods The study comprised 771 participants from the Danish, population-based cross-sectional ‘Health2008’ study. Sleep duration and sleep quality were measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA1c, two measures of insulin sensitivity (the insulin sensitivity index0,120 and homeostasis model assessment of insulin sensitivity), the homeostasis model assessment of β-cell function and glucose tolerance status. Associations of sleep duration and sleep quality with markers of glucose homeostasis and tolerance were analysed by multiple linear and logistic regression. Results A 1-h increment in sleep duration was associated with a 0.3 mmol/mol (0.3%) decrement in HbA1c and a 25% reduction in the risk of having impaired glucose regulation. Further, a 1-point increment in sleep quality was associated with a 2% increase in both the insulin sensitivity index0,120 and homeostasis model assessment of insulin sensitivity, as well as a 1% decrease in homeostasis model assessment of β-cell function. Conclusions In the present study, shorter sleep duration was mainly associated with later alterations in glucose homeostasis, whereas poorer sleep quality was mainly associated with earlier alterations in glucose homeostasis. Thus, adopting healthy sleep habits may benefit glucose metabolism in healthy populations.

Serum 25(OH)D and incident type 2 diabetes: a cohort study

Abstract: Mild to moderate vitamin D insufficiency has been proposed as a risk factor for several common chronic diseases including type 2 diabetes. This study aimed to examine the association between serum 25-hydroxy vitamin D (25(OH)D) and incident diabetes. The MONICA10 cohort consists of 2656 participants (men and women aged 41–71 years) who participated in a 10-year follow-up examination during 1993–1994 as part of the MONICA 1 population survey. A total of 2571 participants free of diabetes at baseline and with successful measurement of serum 25(OH)D were included in the current study. The Danish National Diabetes register enabled identification of 288 cases of incident diabetes during follow-up (median: 16.4 years). Data were analysed by Cox proportional hazard models and associations were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Serum 25(OH)D was inversely associated with incident diabetes adjusted for potential confounders (HR per 25 nmol/l=0.83; 95% CI: 0.72–0.95; P=0.009). A statistically significant interaction was observed between 25(OH)D and waist circumference (WC) (Pinteraction=0.042) suggesting an association in persons with a high WC (HR (95%CI) per 25 nmol/l=0.74 (0.63–0.88), 218 incident cases) and not in persons with a normal WC (HR (95%CI) per 25 nmol/l=0.98 (0.78–1.24), 70 incident cases). Low serum 25(OH)D was associated independently with incident diabetes. The inverse association was only found in overweight-obese and not in normal weight individuals, suggesting that obesity may modify the effect of vitamin D status on the risk of diabetes.

The association between contact sensitization and atopic disease by linkage of a clinical database and a nationwide patient registry.

Abstract: Background Experimental studies have shown that individuals with atopic dermatitis are likely to have suppressed contact sensitivity secondary to their disease whereas some clinical and epidemiological studies have shown that individuals with atopic dermatitis might have a higher prevalence of contact sensitization than controls. The objective was to study the association between contact sensitization and, respectively, atopic dermatitis and asthma using clinical databases. Methods Record linkage of two different registers was performed: (i) a tertiary hospital register of dermatitis patient's patch tested for contact sensitivity and (ii) the Danish National Patient Register containing nationwide hospital discharge diagnoses and outpatient contacts. Results An inverse association was found between contact sensitization and, respectively, presumed severe atopic dermatitis (OR, 0.70; 95% CI, 0.61–0.81) and asthma (OR, 0.61; 95% CI, 0.42–0.90) when linkage was performed. Inverse associations were found for all groups of chemicals and metals except for sensitization to fragrances and topical drugs where positive associations were identified. A significant positive association between fragrance sensitization and presumed mild–moderate atopic dermatitis was also found when data from hospital register only were used, suggesting an overall higher prevalence of fragrance sensitization in patients with atopic dermatitis. Conclusions Our findings support that patients with severe atopic dermatitis and asthma have an overall lower prevalence of contact sensitization when compared with controls, whereas mild-to-moderate disease does not suppress contact sensitization. The prevalence of contact sensitization to fragrance chemicals was higher in patients with atopic dermatitis. Patients should be instructed to avoid scented moisturizers and products containing highly sensitizing substances.

Filaggrin loss-of-function mutation R501X and 2282del4 carrier status is associated with fissured skin on the hands: results from a cross-sectional population study.

Abstract: Summary Background Filaggrin metabolites act as osmolytes and are important for skin hydration. Carriers of filaggrin loss-of-function mutations have a higher prevalence of atopic dermatitis and dry skin. There is also evidence to suggest that filaggrin mutations increase the risk of hand eczema in atopic individuals. In our clinic, we have observed a distinct phenotype of hand eczema in patients with filaggrin mutation carrier status, characterized by fissured dermatitis on the dorsal aspect of the hands and with only sparse involvement of the palms including fine scaling. Objectives To investigate whether filaggrin loss-of-function mutations are associated with skin fissures on the hands and/or fingers in the general population. Methods Participants in a population-based study were questioned about skin symptoms, genotyped for filaggrin mutation, patch tested for nickel allergy and skin prick tested. Results In an adjusted logistic regression analysis, filaggrin mutation status was significantly associated with fissured skin on the hands and/or fingers in adults (odds ratio 1·93, 95% confidence interval 1·05–3·55) and showed a nearly significant negative interaction with atopic dermatitis (P = 0·055), suggesting that the effect was predominantly in subjects without atopic dermatitis. Conclusions Filaggrin loss-of-function mutations seem not only to increase the risk of atopic dermatitis and dry skin but also the risk of fissures on the hands and/or fingers in subjects without atopic dermatitis. Prophylactic emollient therapy should be particularly encouraged in filaggrin loss-of-function mutation carriers.

Exploring the obesity-asthma link: do all types of adiposity increase the risk of asthma?

Abstract: SummaryBackground Obesity and risk of asthma are linked. Different distributions of adiposity, such as visceral, subcutaneous or ectopic adiposity, may affect asthma risk differently. Objective To explore the association of different adiposity types with self-reported asthma, bronchial inflammation and lung function, accounting for possible effect modifiers, such as atopy and gender. Methods In a general population sample of 3471 persons aged 19–72, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by ultrasound, and fat percentage by bio-impedance. Body mass index, waist circumference, waist-to-hip ratio (WHR), bronchial inflammation as fractional expiratory nitric oxide (FeNO), lung function [FEV 1 and forced vital capacity (FVC)], and atopy (specific IgE) were measured. Results All adiposity measures were associated with a higher risk of asthma. The risk estimates (odds ratios, OR, with 95% confidence interval, CI) of current asthma were of similar magnitude for all six adiposity measures ranging between 1.17, CI = 0.98–1.40 (SAT) and 1.51, CI = 1.17–1.95 (WHR). The adiposity-asthma associations were significantly stronger in non-atopics than in atopics. In non-atopics the risk estimates of current asthma ranged between 1.35 CI = 1.08–1.72 and 1.82 CI = 1.34–2.46 for SAT and WHR respectively. Consistent results were obtained using dichothomized adiposity measures (obese vs. non-obsese). The FVC and FEV 1 decreased significantly with increasing adiposity in both atopics and non-atopics, e.g. FVC decreased between 36 mL (CI = 10, 62 mL) and 155 mL (CI = 124, 186 mL) for one unit (standard error) increase of SAT and VAT respectively. Adiposity measures were not associated with atopy and not consistently associated with FeNO levels. Conclusions and Clinical Relevance The effect of adiposity on asthma was mainly seen in non-atopics and did not appear to depend on the distribution of adiposity as reflected by the adiposity measures used in the present study. Increasing adiposity was associated with lower lung function independent of atopic status.

Determinants of Serum Tryptase in a General Population: The Relationship of Serum Tryptase to Obesity and Asthma

Abstract: Background: Recent studies indicate that mast cells are more abundant in the obese state. Total serum tryptase (ST) is a marker of mast cell numbers or activity. Since obesity and a

Vitamin D status and cause-specific mortality: a general population study.

Abstract: Background Vitamin D deficiency is associated with an increased risk of all-cause mortality in observational studies. The specific causes of death underlying this association lack clarity. We investigated the association between vitamin D status and cause-specific mortality.

Interaction between filaggrin null mutations and tobacco smoking in relation to asthma.

Abstract: Background The mechanisms underlying the association between filaggrin ( FLG ) deficiency and asthma are not known. It has been hypothesized that FLG deficiency leads to enhanced percutaneous exposure to environmental substances that might trigger immune responses. We hypothesized that interactions between FLG deficiency and environmental exposures play a role in asthma development. Objective We sought to investigate possible interactions between FLG null mutations and tobacco smoking in relation to asthma. Methods A total of 3471 adults from a general population sample participated in a health examination. Lung function and serum specific IgE levels to inhalant allergens were measured, and information on asthma and smoking was obtained by means of questionnaire. Participants were genotyped for the 2 most common FLG null mutations in white subjects: R501X and 2282del4. Another Danish population was used for replication. Results The FLG null mutation genotype was significantly associated with a higher prevalence of asthma and decreased FEV 1 /forced vital capacity ratio. In logistic regression analyses with asthma as the outcome, a significant interaction was found between FLG null mutations and smoking status ( P = .02). This interaction was confirmed, although it was not statistically significant, in another Danish population study. Interactions between FLG genotype and cumulated smoking exposure were found in relation to asthma ( P = .03) and decreased FEV 1 /forced vital capacity ratio ( P = .03). A 3-way interaction was found among FLG genotype, smoking, and asthma, suggesting that the FLG -smoking interaction mainly played a role in nonatopic subjects. Conclusion FLG null mutations modified the effects of smoking on the risk of asthma. This finding might have implications for risk stratification of the population.

Variations of CHI3L1, levels of the encoded glycoprotein YKL-40 and prediction of fatal and non-fatal ischemic stroke.

Abstract: Background Polymorphisms of CHI3L1 are associated with inter-individual YKL-40 levels and YKL-40 is associated with an increased mortality and is elevated in patients with cardiovascular disease. We investigated the association between single nucleotide polymorphisms (SNPs) of CHI3L1, serum YKL-40 levels and all-cause and cardiovascular mortality and first-time incidence of myocardial infarction, ischemic heart disease (IHD) and stroke. Methodology/Principal Findings 12 SNPs of CHI3L1 were genotyped and serum YKL-40 was measured in 2656 Danes representative of the general population. Median follow-up period was 15 (0–16) years. Admission data and deaths were ascertained from registers from the Danish National Board of Health. Fourth quartile YKL-40 levels were associated with an increased mortality risk of ischemic stroke (HR 2.44 (1.01–5.88), p = 0.041) and so were homozygotes of the minor allele of rs872129 (HR 9.35 (1.25–69.87, p = 0.022)). Both continuous YKL-40 levels and 4th quartile YKL-40 values (>85 ng/ml) were associated with all-cause mortality (HRs 1.22 (95% CI, 1.10–1.35), p<0.0001, and 1.40 (1.15–1.71), p<0.0001), an increased risk of first-time stroke (HR 1.16 (1.01–1.33), p = 0.04, and 1.63 (1.23–2.16), p = 0.001) and a decreased risk of incidence of IHD (HR 0.77 (0.65–0.91), p = 0.002, and 0.61 (0.44–0.85), p = 0.003). Conclusions/Signficance High YKL-40 levels (>85 ng/ml) and rs872129 were associated with an increased mortality risk of ischemic stroke, but high YKL-40 levels were also inverse related with the risk of incidence of IHD. This could be a chance finding but could also elucidate that YKL-40 plays different roles in development of thromboembolisms versus the formation of local thrombosis.

Allergen-specific immunotherapy and risk of autoimmune disease.

Abstract: Purpose of reviewAfter 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic.Recent findingsSeveral case reports

The immune marker soluble urokinase plasminogen activator receptor is associated with new‐onset diabetes in non‐smoking women and men

Abstract: Diabet. Med. 29, 479–487 (2012) Abstract Aim To explore the putative association of new-onset diabetes and the soluble urokinase plasminogen activator receptor (suPAR), which is a new and stable plasma marker of immune function and low-grade inflammation. This association has been previously suggested by using the less sensitive International Classification of Disease system to detect incident diabetes in the Danish MONICA 10 cohort. Methods The Danish National Diabetes Register enabled more accurate identification of incident diabetes during a median follow-up of 13.8 years in the Danish MONICA 10 cohort (n = 2353 generally healthy individuals). The soluble urokinase plasminogen activator receptor was measured by the ELISA method. To fulfil model assumptions, outcome analyses were stratified by age, and further by smoking, owing to the interaction between the soluble urokinase plasminogen activator receptor and smoking on new-onset diabetes (P < 0.0001). Results New-onset diabetes (n = 182) was associated with increased soluble urokinase plasminogen activator receptor levels (P = 0.013). Among 699 middle-aged (41 and 51 years) and 564 older (61 and 71 years) non-smokers, participants in the upper soluble urokinase plasminogen activator receptor quartile had a sex- and age-adjusted relative risk of 6.01 (95% CI 2.17–16.6, P < 0.0006) and relative risk of 3.25 (95% CI 1.51–6.98, P = 0.0025), respectively, for new-onset diabetes compared with participants in the lowest quartile. This relationship remained significant after additional adjustments for C-reactive protein and leukocytes or fasting glucose and insulin or BMI (P < 0.05). The soluble urokinase plasminogen activator receptor was not related to incident diabetes among smokers (P ≥ 0.85). Conclusions In these explorative analyses, the soluble urokinase plasminogen activator receptor associated independently with incident diabetes in non-smokers, supporting an immune origin of Type 2 diabetes. Competing disease risk may explain lack of association among smokers.

Epidemiology of non-hereditary angioedema.

Abstract: The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C(1) esterase inhibitor protein (functional C(1) INH). The general population sample (44% response rate) reported a lifetime prevalence of 7.4% for angioedema. In both groups symptoms were most frequent in the lips, head, neck, eyes and tongue. In the C(1) INH test normal group angioedema was still active at the time of the study in 53% of the patients, and 36% reported symptoms in the throat, 23% in the abdominal area, 17% had diarrhoea, 11% had vomiting and 6% fainted during attacks. Non-hereditary angioedema has high lifetime prevalence and becomes chronic in approximately 50% of affected patients. Symptoms in the larynx and throat, as well as non-specific symptoms, such as dizziness and abdominal pain, were more frequent than previously reported.

Genetic Variant SCL2A2 Is Associated with Risk of Cardiovascular Disease – Assessing the Individual and Cumulative Effect of 46 Type 2 Diabetes Related Genetic Variants

Abstract: Aim To assess the individual and combined effect of 46 type 2 diabetes related risk alleles on incidence of a composite CVD endpoint.

Atopic diseases by filaggrin mutations and birth year.

Abstract: Background The prevalence of atopic disorders has increased in recent years. The pathogenesis is complex with genetic and environmental risk factors. Filaggrin loss-of-function mutations are common and associated with atopic disorders. We investigated whether the prevalence of filaggrin mutations increased in different birth cohorts in adults from the general population in Denmark. Methods Cross-sectional questionnaire and filaggrin gene mutation (R501X and 2282del4) data from 3335 18- to 69-year-old adults were available for analyses. Results The effect of filaggrin mutations on the prevalence of atopic diseases, albeit not statistically significant, depended mostly on birth year for atopic dermatitis (AD). A nonsignificant increase in the prevalence of filaggrin mutations was noted across birth year groups reporting AD, with 12.9% in adults born in 1936–1949 and 19.0% born in 1976–1988. Conclusions If confirmed in other populations, the observed increase suggests that mutation carriers have been more susceptible to environmental changes accentuating the rise in AD prevalence.

The filaggrin null genotypes R501X and 2282del4 seem not to be associated with psoriasis: results from general population study and meta-analysis.

Abstract: Background Psoriasis vulgaris could be associated with the filaggrin null genotype since certain known susceptibility loci for psoriasis are shared with susceptibility loci for atopic dermatitis. Furthermore, filaggrin expression is lowered in psoriatic skin lesions but normally expressed in uninvolved skin. So far five relatively small patient-based case-control studies have rejected a possible association between psoriasis and the two most prevalent filaggrin null mutations, 2282del4 and R501X. Objectives To reinvestigate a possible association between psoriasis and filaggrin null mutation status by using cross-sectional general population questionnaire data. Also, to perform a meta-analysis including published studies that investigated the relation between filaggrin gene mutations R501X and 2282del4, respectively, and psoriasis vulgaris. Methods Between June 2006 and May 2008, a cross-sectional study was performed in the general population in Copenhagen. A random sample of 7931 subjects aged 18–69 years was invited to participate in a general health examination including a questionnaire and 3471 (43.7%) participated. A total of 3335 (96.1%) individuals were filaggrin genotyped for the 2282del4 and R501X mutations. A meta-analysis was undertaken to investigate the relation between filaggrin gene mutations and psoriasis vulgaris. Results The prevalence of self-reported psoriasis was 6.7% among the 3240 respondents. The prevalence of the R501X and 2282del4 filaggrin null genotypes was 9.3% in subjects who reported psoriasis and 8.0% in subjects who did not report psoriasis (OR = 1.28; 95% CI = 0.74–1.89; P = 0.78). The meta-analysis found no association between the filaggrin null genotypes R501X and 2282del4 and psoriasis (OR = 1.04; 95% CI = 0.81–1.35). Conclusions Psoriasis was not associated with the R501X and 2282del4 filaggrin null genotypes in a general population study and in a meta-analysis on published studies.

Minor interference of cross-reactive carbohydrates with the diagnosis of respiratory allergy in standard clinical conditions.

Abstract: Background: Immunoglobulin E (IgE) to N-glycans from plant and invertebrate glycoproteins induces extensive in vitro cross-reactivity. This study investigates the prevalence and dia

The Association between genetic variations of CHI3L1, levels of the encoded glycoprotein YKL-40 and the lipid profile in a Danish population.

Abstract: Background: The inflammatory biomarker YKL-40 seems to play a role in atherosclerosis and is elevated in patients with obesity, cardiovascular disease and type 2 diabetes. Single nucleotide polymorphisms (SNPs) of the YKL-40 encoding gene, CHI3L1, are associated with inter-individual YKL-40 levels. One study has described an association between a promoter polymorphism of CHI3L1 and levels of low density lipoprotein. The objective of this study was to evaluate the influence of YKL-40 on lipid parameters by determining the association between polymorphisms of CHI3L1, serum YKL-40 and levels of the differentiated lipid profile in a Danish general population. Methodology/Principle Findings: 12 SNPs of CHI3L1 were genotyped, and serum YKL-40 and parameters of the lipid profile were measured in 2,656 Danes. Lipid profile and genotypes were available in another Danish population (n=6,784) for replication. Cholesterol and triglyceride levels increased with increasing YKL-40 quartile (both p,0.0001), and YKL-40 correlated with triglyceride levels (b=0.15, p,0.0001). Low density lipoprotein levels increased slightly from the 1 st to the 3 rd quartile (p=0.006). The highest YKL-40 quartile was associated with a greater risk of hypercholesterolemia compared to the lowest YKL-40 quartile (odds ratio 1.36, p=0.009). Minor homozygosity of rs12123883 was associated with higher triglyceride levels (p=0.022) and a higher prevalence of low high density lipoprotein (p=0.012), but these associations could not be confirmed in the replication population. Conclusions/Significance: Serum YKL-40 correlates with triglyceride levels in a representative group of the general Danish population. No consistent associations between SNPs of CHI3L1 and lipid levels could be documented.

Insulin-like growth factor I and anthropometric parameters in a Danish population.

Abstract: During the last decade several studies indicated that low insulin-like growth factor (IGF) I levels are related to higher risk of cardiovascular disease and mortality. Obesity represents one further main cardiovascular risk factor which might also be related to IGF-I. The objective of the present study was to analyse the associations between anthropometric measures and IGF-I levels in a population-based sample. From the Danish cross-sectional Health2006 study 3 328 subjects (1 835 women; 1 493 men) aged 19–72 years were included in the analyses. Serum IGF-I levels were determined by an immunoassay. Body height, weight as well as waist and hip circumferences were measured. Body-mass-index, waist-to-hip ratio and waist-to-height ratio were calculated. Circulating IGF-I levels were inversely associated with all anthropometric markers as evaluated by linear regression adjusting for age, alcohol consumption, smoking and physical activity. Our large cross-sectional study suggests that IGF-I may serve as the link between obesity and mortality although any causal relation cannot be inferred and longitudinal analyses are needed to clarify the causal relation.

Individuals who are homozygous for the 2282del4 and R501X filaggrin null mutations do not always develop dermatitis and complete long-term remission is possible.

Abstract: Background About 8–10% of the general population in Europe carry a null mutation in the filaggrin gene which is associated with early onset of atopic dermatitis as well as persistence into adulthood. No studies have investigated whether individuals with the homozygous filaggrin null genotype always develop dermatitis. Objectives The aim of this study was to describe the natural history of individuals with no filaggrin expression. Materials Three study populations were included: (i) a random sample of 3335 subjects aged 18–69 years from the general population in Copenhagen who underwent general health examination; (ii) a total of 499 patients seen in our dermatitis clinic since 2009 and who were filaggrin genotyped as a part of the routine diagnostic work up; and (iii) a prospective, longitudinal, birth cohort study of 411 children born to mothers with a history of asthma. Filaggrin genotyping was performed for the 2282del4 and R501X mutations. Results Filaggrin homozygous ⁄ compound heterozygous individuals accounted for 0.3% of adults, 3% of dermatitis patients and 0.7% of children. Respectively, one of nine adults and one of three children never experienced dermatitis until now. All hospital patients had atopic dermatitis with onset during (early) childhood. Year-long complete remission was observed in half of patients. Conclusions The natural history of individuals with the filaggrin null genotype is fairly good in the sense that they may not develop dermatitis at all, and if they do, they may experience complete remission.