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Showing papers by "Terho Lehtimäki published in 2009"


Journal ArticleDOI
TL;DR: A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder, and autism, while the reciprocal microdeletion was associated only with autism and developmental disorders.
Abstract: Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1, 2, 3. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 10-5, OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 10-7), bipolar disorder (P = 0.017) and autism (P = 1.9 10-7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 10-13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).

689 citations


Journal ArticleDOI
17 Aug 2009-Analyst
TL;DR: It is demonstrated that the NMR data as such reveal associations between systemic metabolic phenotypes and the metabolic syndrome, paving the way for this technology in large-scale clinical and epidemiological studies.
Abstract: A high-throughput proton (1H) nuclear magnetic resonance (NMR) metabonomics approach is introduced to characterise systemic metabolic phenotypes. The methodology combines two molecular windows that contain the majority of the metabolic information available by 1H NMR from native serum, e.g. serum lipids, lipoprotein subclasses as well as various low-molecular-weight metabolites. The experimentation is robotics-controlled and fully automated with a capacity of about 150–180 samples in 24 h. To the best of our knowledge, the presented set-up is unique in the sense of experimental high-throughput, cost-effectiveness, and automated multi-metabolic data analyses. As an example, we demonstrate that the NMR data as such reveal associations between systemic metabolic phenotypes and the metabolic syndrome (n = 4407). The high-throughput of up to 50 000 serum samples per year is also paving the way for this technology in large-scale clinical and epidemiological studies. In contradiction to single ‘biomarkers’, the application of this holistic NMR approach and the integrated computational methods provides a data-driven systems biology approach to biomedical research.

513 citations


Journal ArticleDOI
TL;DR: The results suggest that the effect of the FTO genotype on BMI becomes evident only after age 7 yr, and suggest thatThe FTO gene is not directly associated with energy intake or physical activity.
Abstract: Context: A common variant in the FTO gene, rs9939609, associates with body mass index (BMI) in adults and in children aged 7 yr or older. Objective: Our aim was to examine the associations of the FTO genotype with BMI, cardiovascular risk factors, energy intake, and leisure-time physical activity in children followed up since infancy. Methods: Healthy participants of the STRIP Study, genotyped for rs9939609, were followed from age 7 months (n = 640) to 15 yr (n = 438). The children were randomly assigned to lifestyle intervention and control groups. Height, weight, blood pressure, and serum lipids were measured annually. Food records and physical activity index were obtained at age 15 yr. Results: The FTO genotype did not associate with BMI in children younger than 7 yr of age. From age 7 yr onward, the children homozygous for the A allele had progressively higher BMI than the children with one or two T alleles (P = 0.029 for FTO by age interaction). Furthermore, in longitudinal, BMI Z-score-adjusted anal...

174 citations


Journal ArticleDOI
TL;DR: Obesity, high low-density lipoprotein cholesterol, and high insulin level predicted IMT progression in young adults, and there was no evidence that MetS would predictIMT progression more than expected from the sum of its risk components.
Abstract: Background— Conventional risk factors and metabolic syndrome (MetS) are cross-sectionally associated with subclinical atherosclerosis in young adults. We evaluated the relations of conventional risk factors and MetS to the 6-year progression of carotid intima-media thickness (IMT) in a population of young adults. Results and Methods— The study included 1809 subjects (aged 32±5 years) who had IMT measured in 2001 and 2007. Risk factor measurements included low-density lipoprotein cholesterol, body mass index, C-reactive protein, smoking, and family history of coronary disease in addition to MetS components. We used European Group for the Study of Insulin Resistance, revised National Cholesterol Education Program, and International Diabetes Federation definitions to diagnose MetS in 2001. Waist circumference (P<0.0001), low-density lipoprotein cholesterol (P=0.01), and insulin (P=0.003) were directly associated with IMT progression in a multivariable model adjusted for age, sex, and baseline IMT (model R2=2...

172 citations


Journal ArticleDOI
TL;DR: None of the seven single nucleotide polymorphisms was associated with major depressive disorder or with treatment response in the study population of Finnish individuals.
Abstract: Genes that regulate the serotonin signalling system are potential targets for research in the aetiology of mood disorders and also in the treatment response of serotonin reuptake inhibitors. In this study, we evaluated the association of seven serotonin signal transduction-linked single nucleotide polymorphisms [HTR1A (rs6295), HTR2A (rs6313, rs6311 and rs7997012), HTR6 (rs1805054), TPH1 (rs1800532) and TPH2 (rs1386494)] with major depressive disorder and/or treatment outcome with serotonin reuptake inhibitors. Patients who met the criteria for major depressive disorder were treated for 6 weeks with fluoxetine, paroxetine or citalopram. The treatment response was evaluated with the Montgomery-Asberg Depression Rating Scale, and according to predefined response criteria, the patients were divided into responders, nonresponders, remitters and nonremitters. Altogether, 86 patients completed the entire study according to the study protocol. We had also a control population (N = 395) of healthy blood donors. None of the seven single nucleotide polymorphisms was associated with major depressive disorder or with treatment response in our study population of Finnish individuals.

117 citations


Journal ArticleDOI
TL;DR: The liver responds to a 6-wk period of calorie restriction with a parallel reduction in lipid uptake and storage, accompanied by enhancement of hepatic insulin sensitivity and clearance.
Abstract: Objective: Weight loss has been shown to decrease liver fat content and whole-body insulin resistance. The current study was conducted to investigate the simultaneous effects of rapid weight reduction with a very-low-calorie diet on liver glucose and fatty acid metabolism and liver adiposity. Hypothesis: We hypothesized that liver insulin resistance and free fatty acid uptake would decrease after weight loss and that they are associated with reduction of liver fat content. Design: Thirty-four healthy obese subjects (body mass index, 33.7 ± 8.0 kg/m2) were studied before and after a very-low-calorie diet for 6 wk. Hepatic glucose uptake and endogenous glucose production were measured with [18F]fluorodeoxyglucose during hyperinsulinemic euglycemia and fasting hepatic fatty acid uptake with [18F]fluoro-6-thia-heptadecanoic acid and positron emission tomography. Liver volume and fat content were measured using magnetic resonance imaging and spectroscopy. Results: Subjects lost weight (11.2 ± 2.9 kg; P < 0.000...

114 citations


Journal ArticleDOI
TL;DR: Findings provide strong evidence for the involvement of catalytically activeADAM-9, ADAM-15, and ADam-17 in advanced atherosclerosis, most notably associated with cells of monocytic origin.
Abstract: Background and aims. The expression of disintegrin and metalloprotease ADAM-9, ADAM-15, and ADAM-17 has been associated with cell-cell, cell-platelet, and cell-matrix interactions and inflammation. They are possibly implicated in the pathophysiology of atherosclerosis. Methods and results. Whole-genome expression array and quantitative real-time polymerase chain reaction (PCR) analysis confirmed that ADAM-9, ADAM-15, and ADAM-17 are upregulated in advanced human atherosclerotic lesions in samples from carotid, aortic, and femoral territories compared to samples from internal thoracic artery (ITA) free of atherosclerotic plaques. Western analysis indicated that the majority of these ADAMs were in the catalytically active form. ADAM-9, ADAM-15, and ADAM-17-expressing cells were shown to co-localize with CD68-positive cells of monocytic origin in the atherosclerotic plaques using immunohistochemistry and double-staining immunofluorescence analysis. Co-localization was demonstrated in all vascular territories. In the carotid territory, cells expressing the ADAMs co-distributed also with smooth muscle cells and, in femoral territory, with CD31-positive endothelial cells, indicating that the ADAM expression pattern depends on vascular bed territory. Conclusions. Present findings provide strong evidence for the involvement of catalytically active ADAM-9, ADAM-15, and ADAM-17 in advanced atherosclerosis, most notably associated with cells of monocytic origin.

82 citations


Journal ArticleDOI
TL;DR: Abdominal adipose tissue perfusion and rGU are not related in obesity and rapid weight loss decreases perfusion through adipose tissues depots but has no influence on rGU demonstrating the ‘sink’ role of adiposes tissue.
Abstract: Objective. Rapid weight loss with very-low-calorie diet (VLCD) is known to improve insulin sensitivity and decrease adipose tissue masses. The aim was to investigate the effects of VLCD on adipose tissue regional glucose uptake (rGU) and perfusion and their association with adipokines.Research design and methods. Sixteen healthy obese (body mass index 33±1.1 kg/m2) subjects underwent VLCD for 6 weeks. RGU and perfusion were measured using [18F]-fluoro-deoxy-glucose, [15O]H2O and positron emission tomography.Results. Blood-flow and rGU expressed per gram of adipose tissue were higher in visceral fat compared to abdominal subcutaneous fat (P<0.01 for both). Dieting decreased weight by 11±0.9 kg (P<0.0001). Visceral adipose fat decreased by 25% (P<0.001) and abdominal subcutaneous fat by 16% (P<0.001). Whole body insulin sensitivity increased by 33% (P<0.01). Perfusion of both fat depots decreased (P<0.001), while rGU remained unchanged. Among the adipokines, leptin and interleukin-6 levels seemed to be asso...

67 citations


Journal Article
TL;DR: Valvular calcification is common in CKD, and is closely associated with findings of intimal arterial disease, which is five-fold more common in diabetic patients than among non-diabetics.
Abstract: BACKGROUND AND AIM OF THE STUDY Cardiovascular calcification is a common complication in patients with chronic kidney disease (CKD). The study aim was to identify the characteristics and risk factors of valvular calcification, and its relationship to atherosclerosis, in CKD. METHODS In this cross-sectional study, a total of 135 patients with CKD (mean age 52 +/- 11 years) included 58 pre-dialysis patients, 36 dialysis patients, and 41 renal transplant recipients. A control group of 58 subjects was also examined. The characteristics of valvular calcification were assessed using transthoracic echocardiography. RESULTS The combined prevalences of mitral or aortic valve calcification were 31% in pre-dialysis patients, 50% in dialysis patients, 29% in renal transplant recipients, and 12% in controls (p = 0.001). The prevalences of mitral annular calcification were 17%, 31%, 27% and 2%, respectively (p = 0.001). In multivariate analysis, the risk factors for valvular calcification in CKD were age, duration of dialysis treatment and interleukin-6 level. Mitral annular calcification proved to be five-fold more common in diabetic patients than among non-diabetics. A close association between valvular calcification and patients with or without increased carotid intima-media thickness (44% versus 15%, p < 0.001), carotid plaque (77% versus 49%, p = 0.002), calcified carotid plaque (65% versus 26%, p = 0.001), coronary artery disease (40% versus 15%, p = 0.003) and peripheral arterial disease (46% versus 9%, p < 0.001) was found. CONCLUSION Valvular calcification is common in CKD, and is closely associated with findings of intimal arterial disease. The presence of inflammation and the duration of dialysis treatment contribute to this complication. Diabetes is also a prominent risk factor for mitral annular calcification in CKD.

67 citations


Journal ArticleDOI
TL;DR: Whether quantification of T‐wave alternans (TWA) enhances this parameter's capacity to evaluate the risk for total and cardiovascular mortality and sudden cardiac death (SCD) is examined.
Abstract: Introduction: We examined whether quantification of T-wave alternans (TWA) enhances this parameter's capacity to evaluate the risk for total and cardiovascular mortality and sudden cardiac death (SCD). Methods and Results: The Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (n = 2,119; 1,342 men and 777 women) with a clinically indicated exercise test with bicycle ergometer. TWA (time domain-modified moving average method) was analyzed from precordial leads, and the results were grouped in increments of 10 μV. Hazard ratios (HR) for total and cardiovascular mortality and SCD were estimated for preexercise, routine exercise, and postexercise stages. Cox regression analysis was performed. During follow-up of 47.1 ± 12.9 months (mean ± standard deviation [SD]), 126 patients died: 62 were cardiovascular deaths, and 33 of these deaths were sudden. During preexercise, TWA ≥ 20 μV predicted the risk for total and cardiovascular mortality (maximum HR >4.4 at 60 μV, P < 0.02 for both). During exercise, HRs of total and cardiovascular mortality were significant when TWA measured ≥50 μV, with 90 μV TWA yielding maximum HRs for total and cardiovascular death of 3.1 (P = 0.03) and 6.4 (P = 0.002), respectively. During postexercise, TWA ≥60 μV indicated risk for total and cardiovascular mortality, with maximum HR of 3.4 at 70 μV (P = 0.01) for cardiovascular mortality. SCD was strongly predicted by TWA levels ≥60 μV during exercise, with maximum HR of 4.6 at 60 μV (P = 0.002), but was not predicted during pre- or postexercise. Conclusion: Quantification of TWA enhances its capacity for determination of the risk for total and cardiovascular mortality and SCD in low-risk populations. Its prognostic power is superior during exercise compared to preexercise or postexercise.

63 citations


Journal ArticleDOI
TL;DR: Post-exercise assessment of TWA using the MMA method is a strong, independent predictor of risk in patients with coronary artery disease, and the 20- microV cutpoint appears to be most suitable in higher-risk patients, whereas the 60-microV cut point appears more appropriate when TWA is used as a single screening test in those at lower risk.

Journal ArticleDOI
TL;DR: Reduced HRR and heightened TWA powerfully predict risk for cardiovascular and all-cause death in a low-risk population, which could aid in screening of general populations during routine exercise protocols as well as improve insights into pathophysiology.

Journal ArticleDOI
TL;DR: Metabolic syndrome provides additional information on a person's risk for early atherosclerosis beyond FRS in women but not in men, and is an independent determinant of CIMT in both sexes.

Journal ArticleDOI
TL;DR: This work investigated which factors explain the variation in SAA and analysed whether SAA could be associated with preclinical atherosclerosis.
Abstract: Background Serum amyloid A (SAA) is a sensitive marker of inflammation and its elevation has been implicated in obesity and in cardiovascular disease, yet data on its regulation in young adults or on its role in early atherosclerosis is scarce We investigated which factors explain the variation in SAA and analysed whether SAA could be associated with preclinical atherosclerosis Methods Serum amyloid A levels were measured in participants of the Cardiovascular Risk in Young Finns Study (n = 2280, n = 1254 women, n = 1026 men) Correlates and determinants of SAA were analysed and the effect of SAA on subclinical atherosclerosis, measured as intima-media thickness (IMT) and carotid artery compliance, was evaluated with risk-factor adjusted models Results Serum amyloid A correlated directly and independently of BMI with C-reactive protein (CRP), waist circumference and leptin in both sexes, with total cholesterol, LDL cholesterol and ApolipoproteinA1 (ApoA1) in women and with triglycerides, insulin levels and insulin resistance in men Use of combined oral contraceptives and intrauterine device was also associated with SAA levels Determinants for SAA included CRP, leptin and ApoA1 in women, and CRP, leptin and HDL cholesterol in men SAA levels correlated with carotid compliance in both sexes and with IMT in men, yet SAA had no independent effect on IMT or carotid compliance in multivariable analysis Conclusions Serum amyloid A was associated with several metabolic risk factors but was not an independent predictor of IMT or carotid artery compliance Further longitudinal studies will show whether SAA holds a prognostic value as a risk marker, analogously to CRP

Journal ArticleDOI
TL;DR: The results suggest that norepinephrine may modify the severity of perinatal serotonergic symptoms, and the COMT 1947G>A polymorphism may affect the occurrence of respiratory distress symptoms in infants with prenatal SSRI-exposure via a mechanism involving prolactin.

Journal ArticleDOI
TL;DR: Adult men who have been breast fed have better brachial endothelial function compared to men who has been formula fed, and breast feeding was not significantly associated with IMT or CAC in multivariable models.
Abstract: Breast feeding in infancy and arterial endothelial function later in life. The Cardiovascular Risk in Young Finns Study

Journal ArticleDOI
TL;DR: The results suggest that IL6 -174 G>C modifies the levels of several metabolic risk factors of atherosclerosis in men, and was not associated with carotid artery compliance, intima media thickness or CRP.

Journal ArticleDOI
TL;DR: Hypertension interacts with IL-18 gene promoter -137 G/C polymorphism, affecting the risk of SCD and the development of coronary atherosclerosis.
Abstract: Aims The interleukin 18 (IL-18) gene has a single nucleotide promoter region (−137) G-to-C polymorphism (rs187238) which leads to attenuated transcriptional activity of the gene and to lower production of pro-atherogenic IL-18. The C allele of this polymorphism is associated with a lower risk of sudden cardiac death (SCD). We examined the process by which this polymorphism alters the risk of SCD and coronary artery disease (CAD) by analysing the interactions between this polymorphism and environmental factors. Methods and results TaqMan 5′ nuclease assay was used to genotype the study population of the Helsinki Sudden Death Study, comprising medicolegal autopsies of 700 men. According to adjusted logistic regression analysis, there was a significant interaction between IL-18 genotype and hypertension impacting on the risk of SCD due to coronary heart disease (CHD) ( P = 0.011) and the severity of autopsy-verified CAD ( P = 0.026). Among GG homozygotes, hypertension was a major risk factor for SCD due to CHD [adjusted odds ratio (OR) 3.75 with 95% CI 1.78–7.91, P < 0.001] and hypertension also associated with larger coronary atherosclerotic plaque areas ( P = 0.002) and the occurrence of complicated plaques (adjusted OR 8.38 with 95% CI 2.39–29.33, P < 0.001). Among C allele carriers, hypertension was not a significant risk factor for CHD-related SCD or CAD and did not associate with the development of coronary atherosclerotic plaques. According to gene expression analysis of atherosclerotic tissue samples obtained from live patients, hypertension also interacted significantly with IL-18 genotype affecting the expression of IL-18 ( P = 0.030) mRNA and interferon-γ mRNA ( P = 0.004). Conclusion Hypertension interacts with IL-18 gene promoter −137 G/C polymorphism, affecting the risk of SCD and the development of coronary atherosclerosis.

Journal ArticleDOI
TL;DR: Serum and CSF apoE concentrations did not differ between VD patients and contols, and the results suggest that APoE plays no role in the development of VD.
Abstract: We used the NINDS-AIREN criteria to diagnose vascular dementia (VD), and compared apolipoprotein E (apoE) allele frequencies and apoE concentrations in serum and cerebrospinal fluid (CSF) between patients with possible (n = 19) and probable (n = 33) VD and controls (n = 105). There was no difference in apoE4 frequency between patients with probable VD and controls. Serum and CSF apoE concentrations did not differ between VD patients and controls. Our results suggest that apoE plays no role in the development of VD.

Journal ArticleDOI
TL;DR: IL6 -174 allele G homozygozity associates with beneficial profile of early predictors of atherosclerosis such as high CAC, HDL-C and apoA1 as well as low systolic and diastolic blood pressure in men.

Journal ArticleDOI
TL;DR: ECT may able to counteract a putative genetically driven worse depressive phenotype, and may be associated with the severity of treatment-resistant depression.

Journal ArticleDOI
TL;DR: CRP gene allelic variation is associated with serum CRP levels as well as hypertension in Turkish adults and no haplotype association was observed for MetS or its components.

Journal ArticleDOI
TL;DR: The findings suggest that the DRD2 may have an environmentally moderated impact on Novelty seeking and that the origins of such an association may lie already in childhood.
Abstract: Preliminary evidence suggests that there may be longitudinal interactions between environmental and genetic factors in predicting Novelty seeking. We have previously found in small and selected subsample from the Cardiovascular Risk in Young Finns study, that an association between the polymorphism of dopamine receptor D4 was moderated by the childhood environment, as indexed by hostile maternal child-rearing. We wanted to replicate this finding in a population based sample of 1,114 men and women using another candidate gene of dopaminergic system, that is, the dopamine receptor D2 (DRD2). The child-rearing environment of the participants was assessed by their mothers when the participants were children or adolescents, and adulthood Novelty seeking was self-rated by the participants 17 and 21 years later at the ages of 24–39. Genotyping of DRD2 C32806T (rs 1800497) was performed using TaqMan 5′nuclease assay. DRD2 was not directly associated with Novelty seeking, but there was a significant DRD2 × strict maternal disciplinary style interaction in predicting Novelty seeking (F = 7.08, P = 0.008). The interaction showed that when the child-rearing environment was punitive, participants carrying any A1 allele of the DRD2 gene had higher scores on Novelty seeking than carriers of the A2/A2 genotype. The genotype had no effect on Novelty seeking when the childhood environment was more favorable. The findings suggest that the DRD2 may have an environmentally moderated impact on Novelty seeking and that the origins of such an association may lie already in childhood. © 2008 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: The rs1800588 is associated with serum lipid and apolipoprotein concentrations, especially in women, but does not seem to be a determinant of brachial artery FMD, carotid IMT, or CAC in young healthy adults.
Abstract: The common C-480T polymorphism (rs1800588) of the hepatic lipase gene (LIPC) has been associated with high-density lipoprotein (HDL) cholesterol, atherosclerosis, and coronary artery disease. In this study, we examined whether the polymorphism is associated with serum lipid and lipoprotein concentrations, as well as with subclinical atherosclerosis in Young Finns. The participants comprised 2041 men and women (aged 24-39 years) enrolled in the Cardiovascular Risk in Young Finns Study with complete data concerning the rs1800588 polymorphism and serum lipids concentration. All participants underwent an ultrasound examination for brachial artery flow-mediated vasodilatation (FMD) and carotid artery intima-media thickness (IMT) measurement. The marker of arterial elasticity, carotid artery compliance (CAC), was also calculated by means of ultrasound and concomitant brachial blood pressure measurements. In all subjects, serum total cholesterol (p < 0.001), HDL cholesterol (p = 0.006), apolipoprotein AI (apoAI, p < 0.001), and triglyceride (p = 0.009) concentrations increased according to rs1800588 genotype in the order CC, CT, and TT. The same order applied only to apoAI after adjustment for age, body mass index, systolic and diastolic blood pressure, smoking, alcohol consumption, physical activity, diabetes, hypertension, contraceptive hormone use in women, and concentrations of glucose, insulin and C-reactive protein in men and women separately (p = 0.007 and p = 0.003, respectively). The polymorphism was also associated with HDL cholesterol, total cholesterol, and triglyceride levels in women (adjusted p = 0.004, p = 0.007 and 0.02, respectively), but not in men (p was not significant for all). No significant association between the rs1800588 and brachial FMD, carotid IMT, or CAC was found among the entire study population or among women or men separately, with or without adjustment for the above-mentioned factors. The rs1800588 is associated with serum lipid and apolipoprotein concentrations, especially in women, but does not seem to be a determinant of brachial artery FMD, carotid IMT, or CAC in young healthy adults.

Journal ArticleDOI
TL;DR: Evidence is provided from a population of healthy young adults that a common variation in the NOS1AP gene influences cardiac repolarization within the normal physiological range.
Abstract: Background: Common genetic variants in the nitric oxide synthase 1 adaptor protein gene (NOS1AP) and in the HERG potassium channel gene (KCNH2) have been associated with cardiac repolarization in middle-aged and elderly subjects.Aim: We examined the relation between these variants and QT interval duration in a population of healthy young adults.Methods: We measured QT interval duration and genotyped rs10494366 T>G (NOS1AP gene, n=1,842) and rs1805123 A>C (KCNH2 gene, n=1,894) in subjects aged 24–39 years.Results: The NOS1AP variant was significantly related with heart rate-corrected QT interval duration (QTc). Additive regression model adjusting for age, sex, systolic blood pressure, body mass index, alcohol use, and smoking indicated that the G allele was associated with a 3.2 ms (95% confidence interval (CI) 1.7–4.6 ms, P<0.0001) increase in QTc interval duration for each additional copy. The KCNH2 variant was not significantly related with QTc interval duration in the study sample.Conclusion: These fin...

Journal ArticleDOI
TL;DR: Preference for low-lactose milk and milk products may decrease the risk for inadequate Ca intake in those with the C/C− 13910 genotype.
Abstract: Previous evidence suggests that the lactase gene C/T- 13910 polymorphism (rs4988235) is associated with avoidance of milk products and lower Ca intake. We examined whether the consumption of milk and milk products and the intakes of milk nutrients differ between the lactase genotypes from childhood to young adulthood. Subjects belong to the Cardiovascular Risk in Young Finns Study where the first cross-sectional surveys were conducted in 1980 (n 3596), with follow-up studies in 1983, 1986, 1989, 1992 and 2001 (n 2620). The same dietary questionnaire was used throughout the follow-up to collect data on habitual consumption of milk and milk products in all subjects, and daily nutrient intakes were assessed with 48 h dietary recalls in 50 % of the subjects. Subjects with the lactase non-persistence (C/C- 13910) genotype consumed less milk since childhood, but the consumption of other milk products did not differ between the genotypes. In adult females, the lactose content of milk products consumed was lower (P = 0.003), and in both sexes low-lactose and milk-free diets were more common in the C/C- 13910 genotype than in the other genotypes. Inadequate Ca intake was most common in females with the C/C- 13910 genotype as early as in childhood (15-63 %), but in males only in adulthood (24 %). In adult females, preference for low-lactose milk and milk products equalised the differences in Ca intake between the genotypes. Thus, in those with the C/C- 13910 genotype, preference for low-lactose milk and milk products may decrease the risk for inadequate Ca intake.

Journal ArticleDOI
TL;DR: Investigation of the profile of serum fatty acids in newly detected CD before and after treatment with a gluten-free diet found levels of unsaturated and monounsaturated fatty acids were generally increased in subjects with CD compared with those in controls.
Abstract: Objective. Celiac disease (CD) is characterized by villous atrophy with crypt hyperplasia and inflammation of the small intestinal mucosa leading to disturbed epithelial transport. In untreated CD, fat malabsorption can occur. The aim of this study was to investigate the profile of serum fatty acids in newly detected CD before and after treatment with a gluten-free diet. Material and methods. Serum samples were obtained from 50 adults with active CD showing small-bowel mucosal villous atrophy, from the same patients in remission after treatment with a gluten-free diet, and from 59 controls. Serum fatty acids were analyzed by capillary gas-liquid chromatography. Results. Especially the proportions of arachidonic acid (20:4 n-6) and the long-chain polyunsaturated fatty acids of the n-3 family docosapentaenoic acid (22:5 n-3) and docosahexaenoic acid (22:6 n-3) were decreased in subjects with active CD. Serum levels of these fatty acids increased during remission, but still remained significantly lower than ...

Journal ArticleDOI
TL;DR: ADAM8 is a promising candidate to be involved in atherosclerosis, and its 2662 T/G allelic variant significantly associates with advanced atherosclerotic lesion areas and MI.
Abstract: Objective. Previously, we scanned all 23,000 human genes for differential expression between normal and atherosclerotic tissues and found the involvement of ADAM8.Methods. We investigated the expression of ADAM8 mRNA and protein level in human atherosclerotic tissues and non-atherosclerotic internal thoracic arteries as well as the association of ADAM8 2662 T/G single nucleotide polymorphism (SNP) with the extent of coronary atherosclerosis and with the risk of fatal myocardial infarction.Results. ADAM8 mRNA was up-regulated in carotid, aortic, and femoral atherosclerotic plaques (n=24) when compared with non-atherosclerotic arteries. ADAM8 protein expression was increased in advanced atherosclerotic plaques as compared to control vessels wherein it was localized to macrophages and smooth muscle cells The G allele carriers of the ADAM8 2662 T/G SNP had significantly larger areas of fibrotic, calcified, and complicated plaques in coronary arteries (P=0.027, P=0.011, and P=0.011, respectively) and significa...

Journal ArticleDOI
01 May 2009-Bone
TL;DR: Bone loss in young adulthood was more common in males than in females and seemed to occur mainly at the femoral neck, however, calcium intake predicts changes in bone mass more than the lactase genotype.

Journal ArticleDOI
TL;DR: The -930A/G polymorphism modifies the association between cigarette smoking and IMT in young healthy adults and is associated with mean and maximal IMT.