Large-scale search of SNPs for type 2 DM susceptibility genes in a Japanese population

The etiology of type 2 diabetes (DM) is polygenic. We investigated here genes and polymorphisms that associate with DM in the Japanese population. Single-nucleotide polymorphisms (SNPs) of 398 derived from 120 candidate genes were examined for association with DM in a population-based case-control study. The study group consisted of 148 cases and 227 controls recruited from Funagata, Japan. No evident subpopulation structure was detected for the tested population. The association tests were conducted with standard allele positivity tables (chi(2) tests) between SNP genotype frequency and case-control status. The independent association of the SNPs from serum triglyceride levels and body mass index was examined by multiple logistic regression analysis. A value of P<0.01 was accepted as statistically significant. Six genes (met proto-oncogene, ATP-binding cassette transporter A1, fatty acid binding protein 2, LDL receptor defect C complementing, aldolase B, and sulfonylurea receptor) were shown to be associated with DM.     

Dietary intake of selenium and its concentration in breast milk

Selenium concentration was measured in the breast milk of 30 mothers at different stages of lactation and various body mass indices (BMI). For a maternal mean selenium intake meeting 100% of the Recommended Daily Allowance, mean milk selenium concentration was 14.06 ng/mL (range: 10.0–24.7 ng/mL). No significant correlation was found between the concentration of milk selenium with the stage of lactation, BMI, or dietary selenium intake.     

BMI and retinal vascular caliber in children

Objective: In adult populations, changes in retinal vascular caliber have been linked with obesity and metabolic syndrome. We examined the association of BMI and weight with retinal vascular caliber in children. Research Methods and Procedures: This was a school‐based, cross‐sectional study of 768 children, 7 to 9 years old, randomly sampled from the Singapore Cohort Study of the Risk Factors for Myopia. Participants had digital retinal photographs. Retinal vascular caliber was measured using a computer‐based program and combined to provide average calibers of arterioles and venules in that eye. Weight and height were measured using standardized protocol. These data were used to calculate BMI. Results: In this population, the mean retinal arteriolar and venular calibers were 156.40 μm [95% confidence interval (CI), 155.44 to 157.36] and 225.43 μm (95% CI, 224.10 to 226.74) respectively. After controlling for age, gender, race, parental monthly income, axial length, birth weight, and birth length, each 3.1 kg/m² (standard deviation) increase in BMI was associated with a 2.55‐μm (95% CI, 1.21 to 3.89; p < 0.001) larger retinal venular caliber. In multivariable analysis, greater weight was also significantly associated with larger retinal venular caliber. BMI and weight were not associated with retinal arteriolar caliber. Height was not significantly associated with retinal arteriolar or venular caliber. Discussion: Greater BMI and weight are associated with larger retinal venular caliber in healthy children.     

Association of peroxisome proliferator activated receptor-γ gene with non-alcoholic fatty liver disease in Asian Indians residing in north India

Background

Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately studied. We investigated the association of polymorphisms C161T and Pro12Ala of peroxisome proliferator-activated receptor gamma (PPARγ) with clinical and biochemical parameters in Asian Indians with NAFLD.

Methods

In this case–control study, 162 NAFLD cases and 173 controls were recruited. Abdominal ultrasound, clinical and biochemical profiles, fasting insulin levels and value of homeostasis model assessment of insulin resistance were determined. Polymerase chain reaction–restriction fragment length polymorphisms of two polymorphisms were performed. The association of these polymorphisms with clinical and biochemical parameters was analysed.

Results

Higher frequency of Ala and T alleles of PPARγ was obtained in cases. Ala/Ala genotype of PPARγ (Pro12Ala) was associated with significantly higher serum triglycerides (TG), alkaline phosphatase (ALK) and waist–hip ratio in cases as compared to controls. In C161T polymorphism, TT genotype was significantly increased TG (p = 0.04), total cholesterol (p = 0.01), ALK (p = 0.04) and gamma-glutamyl transpeptidase (p = 0.007) in cases. The linkage disequilibrium for these two single-nucleotide polymorphisms of PPARγ was differed in cases (D1 = 0.1; p = 0.006) and controls (D1 = 0.07; p = 0.1). Using a multivariate analysis after adjusting for age, sex and body mass index, the presence of NAFLD was linked to these two polymorphisms (odds ratio 1.64 (95% CI: 1.09–2.45, p = 0.05)].

Conclusion

Asian Indians in north India carrying the alleles Ala and T of PPARγ (Pro12Ala and C161T) polymorphisms are predisposed to develop NAFLD.     

Cardiorespiratory fitness, different measures of adiposity, and cancer mortality in men

Objective: The purpose was to examine the prospective relationship among cardiorespiratory fitness level (CRF), different measures of adiposity, and cancer mortality in men. Research Methods and Procedures: Participants were 38,410 apparently healthy men who completed a comprehensive baseline health examination between 1970 and 2001. Clinical measures included BMI, waist circumference (WC), percent body fat, and CRF quantified as duration of a maximal treadmill exercise test. Participants were divided into fifths of CRF, BMI, WC, and percent body fat. Hazard ratios were computed with Cox regression analysis. Results: During a mean follow‐up period of 17.2 ± 7.9 years, 1037 cancer deaths occurred. Adjusted hazard ratios across incremental BMI quintiles were 1.0, 1.23, 1.15, 1.39, and 1.72; those of WC were 1.0, 1.05, 1.03, 1.31, and 1.64; those of percent body fat were 1.0, 1.24, 1.17, 1.23, and 1.50; and those of CRF were 1.0, 0.70, 0.67, 0.70, and 0.49 (trend p < 0.01 for each). Further adjustment for CRF eliminated the significant trend in mortality risk across percent body fat groups and attenuated the trend in risk across BMI and WC groups. Adjustment of CRF for adiposity measures had little effect on mortality risk. When grouped into categories of fit and unfit (upper 80% and lower 20% of CRF distribution, respectively), mortality rates (per 10,000 man‐years) were significantly lower in fit compared with unfit men within each stratum of BMI, WC, and percent body fat. Discussion: Higher levels of CRF are associated with lower cancer mortality risk in men, independently of several adiposity measures.     

Tubers as fallback foods and their impact on Hadza hunter-gatherers

The Hadza are hunter-gatherers in Tanzania. Their diet can be conveniently categorized into five main categories: tubers, berries, meat, baobab, and honey. We showed the Hadza photos of these foods and asked them to rank them in order of preference. Honey was ranked the highest. Tubers, as expected from their low caloric value, were ranked lowest. Given that tubers are least preferred, we used kilograms of tubers arriving in camp across the year as a minimum estimate of their availability. Tubers fit the definition of fallback foods because they are the most continuously available but least preferred foods. Tubers are more often taken when berries are least available. We examined the impact of all foods by assessing variation in adult body mass index (BMI) and percent body fat (%BF) in relation to amount of foods arriving in camp. We found, controlling for region and season, women of reproductive age had a higher %BF in camps where more meat was acquired and a lower %BF where more tubers were taken. We discuss the implications of these results for the Hadza. We also discuss the importance of tubers in human evolution. Am J Phys Anthropol, 140:751–758, 2009. © 2009 Wiley-Liss, Inc.     

CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.     

Sterol metabolism and protein metabolism are differentially correlated with sarcopenia in Asian Chinese men and women

ObjectivesOur aim was to investigate the prevalence and predictive variables of sarcopenia.MethodsWe recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables.ResultsThe prevalence of sarcopenia and sarcopenic obesity was 9.2%‐16.2% and 0.26%‐9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut‐off value for age was 71 years, which departs from the commonly accepted cut‐off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25‐hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia.ConclusionsOur findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.     

Association between VDR ApaI Polymorphism and Hip Bone Mineral Density Can Be Modified by Body Mass Index： A Study on Postmenopausal Chinese Women

Osteoporosis is a major public health problem for old people. Genetic factors are considered to be major contributors to the pathogenesis of postmenopausal osteoporosis. The vitamin D receptor (VDR) gene is a prominent candidate gene for the regulation of postmenopausal bone mass; however, despite extensive studies, controversy remains regarding its association with postmenopausal body mineral density (BMD) variation. In this study, a total of 260 healthy postmenopausal Chinese women were genotyped at the VDR ApaI locus using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Raw hip BMD was significantly associated with VDR ApaI polymorphism with and without adjusting for age (P=0.015 and 0.040, respectively). This genetic effect can explain 3.32% of hip BMD variation. However, the significant association vanished after correcting for both age and body mass index (BMI) (P=0.169). In addition, we observed a significant association between VDR ApaI polymorphism with unadjusted BMI(P=0.042) or BMI adjusted for age (P=0.049). The raw hip BMD was also found to be significantly correlated with BMI (r=0.517, P=0.0001), with BMI explaining 26.35% of the variation of hip BMD. All of these facts prompt us to conclude that the significant association between the VDR ApaI genotype and hip BMD may be modified by BMI in postmenopausal Chinese women. Our findings may partially explain the earlier inconsistent association results concerning the VDR gene and BMD, and highlight the importance of incorporating covariates such as BMI into osteoporosis association studies.