In this review we give an overview of the physiological functions of a group of ATP binding cassette (ABC) transporter proteins, which were discovered, and still referred to, as multidrug resistanc...

Human Multidrug Resistance ABCB and ABCG Transporters: Participation in a Chemoimmunity Defense System

Adequate sleep is a critical factor for adolescent's health and health-related behaviors. (a) to describe sleep duration in European adolescents from nine countries, (b) to assess the association of short sleep duration with excess adiposity and (c) to elucidate if physical activity (PA), sedentary behaviors and/or inadequate food habits underlie this association. A sample of 3311 adolescents (1748 girls) aged 12.5–17.49 years from 10 European cities in Austria, Belgium, France, Germany, Greece, Hungary, Italy, Spain and Sweden was assessed in the Healthy Lifestyle in Europe by Nutrition in Adolescence Study between 2006 and 2008. We measured anthropometric data, sleep duration, PA (accelerometers and questionnaire), television watching and food habits (Food Frequency Questionnaire). Average duration of daily sleep was 8 h. Shorter sleepers showed higher values of BMI, body fat, waist and hip circumferences and fat mass index (P<0.05), particularly in females. Adolescents who slept <8 h per day were more sedentary, as assessed by accelerometry, and spent more time watching TV (P<0.05). The proportion of adolescents who eat adequate amounts of fruits, vegetables and fish was lower in shorter sleepers than in adolescents who slept ⩾8 h per day, and so was the probability of having adequate food habits (P<0.05). Correlation analysis indicated that short sleep is associated with higher obesity parameters. In European adolescents, short sleep duration is associated with higher adiposity markers, particularly in female adolescents. This association seems to be related to both sides of the energy balance equation due to a combination of increased food intake and more sedentary habits.

Short sleep duration is associated with increased obesity markers in European adolescents: effect of physical activity and dietary habits. The HELENA study

Background: The APOE gene and its protein product is associated with a number of plasma proteins like very-low density lipoprotein (VLDL), high density lipoprotein (HDL) chylomicrons, chylomicron remnants, and plays a crucial role in lipid metabolism. The APOE gene is polymorphic and common alleles (*E2, *E3 and *E4) have been associated with a number of common and complex diseases in different populations. Due to their crucial role in metabolism and clinical significance, it is imperative that allelic variation in different populations is analysed to evaluate the usage of APOE in an evolutionary and clinical context.Aim: We report allelic variation at the APOE locus in three European and four Indian populations and evaluate global patterns of genetic variation at this locus. The large, intricate and unexpected heterogeneity of this locus in its global perspective may have insightful consequences, which we have explored in this paper.Subject and methods: Apolipoprotein E genotypes were determined in four ...

APOE distribution in world populations with new data from India and the UK

Nearly all human complex traits and disease phenotypes exhibit some degree of sex differences, including differences in prevalence, age of onset, severity or disease progression. Until recently, the underlying genetic mechanisms of such sex differences have been largely unexplored. Advances in genomic technologies and analytical approaches are now enabling a deeper investigation into the effect of sex on human health traits. In this Review, we discuss recent insights into the genetic models and mechanisms that lead to sex differences in complex traits. This knowledge is critical for developing deeper insight into the fundamental biology of sex differences and disease processes, thus facilitating precision medicine.

The role of sex in the genomics of human complex traits

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.21847

Increased gallstone risk in humans conferred by common variant of hepatic ATP‐binding cassette transporter for cholesterol

ABCG5 and ABCG8 transporters play an important role in the absorption and excretion of sterols. Missence polymorphisms (Gln604Glu in the ABCG5 and Asp19His, Tyr54Cys, Thr400Lys, and Ala632Val in the ABCG8) in these genes have been described. In 131 males and 154 females whose dietary composition markedly changed and lipid parameters decreased over an 8-year follow-up study (total cholesterol decreased from 6.21+/-1.31 mmol/l in 1988 to 5.43+/-1.06 mmol/l in 1996), these polymorphisms were investigated using PCR. Plasma lipid levels and changes in plasma lipid levels were independent of the Gln604Glu polymorphism in ABCG5 and Asp19His and the Ala632Val polymorphisms in ABCG8. The Tyr54Cys polymorphism influenced the degree of reduction in total plasma cholesterol (delta -0.49 mmol/l in Tyr54 homozygotes vs. delta +0.12 mmol/l in Cys54 homozygotes, p<0.04) and LDL-cholesterol (delta -0.57 mmol/l in Tyr54 homozygotes vs. delta +0.04 mmol/l in Cys54 homozygotes, p<0.03) levels between 1988 and 1996 in females, but not in males. Male Thr400 homozygotes exhibited a greater decrease in total cholesterol (delta -0.90 mmol/l vs. delta -0.30 mmol/l, p<0.02) and LDL-cholesterol (delta -0.62 mmol/l vs. delta -0.19 mmol/l, p<0.04) than Lys400 carriers. No such association was observed in females. We conclude that Tyr54Cys and Thr400Lys variations in the ABCG8 gene may play a role in the genetic determination of plasma cholesterol levels and could possibly influence the gender-specific response of plasma cholesterol levels after dietary changes. These polymorphisms are of potential interest as genetic variants that may influence the lipid profile.

Polymorphisms in ABCG5 and ABCG8 transporters and plasma cholesterol levels.

OBJECTIVES: The body mass index (BMI) has been the most commonly applied clinical measure to characterise body composition in individuals. However, the BMI has been criticised as being an inaccurate measure of body fatness. Recently, a new index reflecting body composition, the Body Adiposity Index (BAI) was proposed. The BAI was calculated using the equation BAI=((hip circumference)/ ((height) 1.5) – 18). AIM: The aim of this study was to compare estimates of body fat content, i.e., body adiposity index (BAI), BMI, waist-hip ratio (WHR) and waist and hip circumferences, with respect to their ability to predict the percentage of body fat (PBF). RESULTS: To select an optimal surrogate for adiposity, we examined the correlation between body adiposity percentage as measured by BIA and several variables, including BAI, BMI and WHR. Correlations ranged from a high of 0.78 for BMI, 0.67 for BAI and 0.66 for waist circumference to a low value of 0.39 for the WHR index. The correlation between PBF and BAI (R=0.67, R 2=0.45, p<0.001) and the correlation between PBF and BMI (R=0.78, R 2=0.60, p<0.001) were of similar magnitude. CONCLUSION: Based on our results and those of other studies, we can say that the BAI index is not a universally valid index that could be used in the place of the BMI index in a Caucasian population; indeed, it would not accurately reflect body fat mass and thus could lead to an increased risk of obesity. Further, WHR index is not a suitable for an estimation of body fat.

Which index best correlates with body fat mass: BAI, BMI, waist or WHR?

Some studies have suggested that there could be an association between the duration of sleep in humans and development of the obesity. We have analyzed the group of the probands (n = 3970, 2038 males and 1932 females, aged 18-65 years), with permanent address in the Central or South Bohemia. We ascertained the relationship between the duration of their sleep (obtained per questionnaire) and body mass index, weight, height, the value of systolic and diastolic blood pressure, heart rate, waist and hip circumference, the values of total-, high density- and low density- cholesterol, thyroid hormone and body exercise performed. The optimal values of the body mass index (and optimal body weight) were associated with the duration of sleep 7 hours per night (P < 0.001). This association was found both in males and females and in both districts. Other anthropometrical and biochemical parameters were not associated with the sleep duration.

/pdf/association-between-duration-of-the-sleep-and-body-weight-45ov3wqp0z.pdf

Association between Duration of the Sleep and Body Weight

Summary Apolipoproteins E and CI are the predominant components of triglyceride-rich lipoproteins. The genes are located in one gene cluster and both are polymorphic. Three allelic (e2, e3 and e4) polymorphisms of the APOE gene influence plasma cholesterol levels. The distribution of these alleles differ between ethnic groups. PCR genotyping was used to determine the APOE and APOCI allele incidence in a representative group of 653 probands (302 men and 351 women) of Czech origin. The observed relative frequencies for the e2, e3 and e4 alleles were 7.1 %, 82.0 % and 10.9 %, respectively, and are similar to other middle European populations. APO e4 carriers have the highest and APO e2 carriers the lowest levels of plasma total cholesterol (p<0.0001) and LDL cholesterol (p<0.0001). The frequency of the insertion (I) allele (HpaI restriction site present) of the APOCI polymorphism was 18.5 %. APOCI I/I homozygotes have the highest level of triglycerides (p<0.003). An almost complete linkage disequilibrium of the insertion allele of APOCI with the APOE alleles e2 and e4 has been detected and suggests that the deletion in the APOCI gene probably follows the deriving of all three APOE alleles on the APO e3 allele background.

/pdf/apolipoprotein-e-and-apolipoprotein-ci-polymorphisms-in-the-4koarizi4g.pdf

Apolipoprotein E and apolipoprotein CI polymorphisms in the Czech population: almost complete linkage disequilibrium of the less frequent alleles of both polymorphisms.

OBJECTIVES A significant inter-individual variability in statin treatment efficacy is likely to have a strong genetic background. A candidate gene with the potential to influence statin treatment efficacy is SLCO1B1. This gene codes for the solute carrier organic anion transporter, which has been shown to regulate the hepatic uptake of statins and some other drugs. MATERIALS AND METHODS The SLCO1B1 rs4149056 (T>C) polymorphism was successfully analysed in a group of 253 patients with dyslipidemia (treated with simvastin or atorvastatin, 10 or 20 mg per day) and 470 healthy normolipidemic controls. The polymorphism was analysed using nested PCR-RFLP. Lipid levels (total, LDL and HDL cholesterol; triglycerides) were analysed before and after 10-13 weeks of treatment. RESULTS After treatment, as expected, there was a significant decrease both in the total cholesterol (7.60±1.36 → 5.37±1.12 mmol/L, p<0.001) and LDL cholesterol (5.04±1.34 → 3.17±0.99 mmol/L, p<0.001) levels. The distribution of the individual genotypes in the patients (TT=61.7%, CT=31.6%, CC=6.7%) was similar (p=0.35) to that of the normolipidemic controls (TT=64.4%, CT=31.3%, CC=4.3%). Homozygous CC males exhibited the lowest (Δ -21.2±7.2%) decrease of total cholesterol in contrast to the females, in whom the same genotype was associated with the highest (Δ -33.5±7.6 %) decrease (p=0.04 for gene-gender interaction). CONCLUSIONS The results of our pilot study suggest possible gender-dependent effects of the rs4149056 variant within the SLCO1B1 gene on statin treatment efficacy.

Lánská

Papers

Polymorphisms in ABCG5 and ABCG8 transporters and plasma cholesterol levels.

Which index best correlates with body fat mass: BAI, BMI, waist or WHR?

Association between Duration of the Sleep and Body Weight

Apolipoprotein E and apolipoprotein CI polymorphisms in the Czech population: almost complete linkage disequilibrium of the less frequent alleles of both polymorphisms.

Possible gene-gender interaction between the SLCO1B1 polymorphism and statin treatment efficacy.