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Effects of variants of 50 genes on diabetes risk among the Chinese population born in the early 1960s.

ABSTRACT: BACKGROUND:Genome-wide association studies have identified loci that significantly increase diabetes risk. This study explored the genetic susceptibility in relation to diabetes risk in adulthood among a Chinese population born in the early 1960s. METHODS:In all, 2129 subjects (833 males, 1296 females) were selected from the cross-sectional 2010 to 2012 China National Nutrition and Health Survey. Fifty diabetes-related single nucleotide polymorphisms (SNPs) were detected. Two diabetes genetic risk scores (GRSs) based on the 50 diabetes-predisposing variants were developed to examine the association of these SNPs with diabetes risk. RESULTS:Associations were found between diabetes risk and SNPs in the MTNR1B (rs10830963), KLHDC5 (rs10842994), GRK5 (rs10886471), cyclindependentkinase 5 regulatory subunit associated protein 1 (rs10946398), adaptorrelated protein complex 3 subunit sigma 2 (rs2028299), diacylglycerol kinase beta/transmembrane protein 195 (rs2191349), SREBF chaperone (rs4858889), ankyrin1 (rs516946), RAS guanyl releasing protein 1 (rs7403531), and zinc finger AN1-type containing 3 (rs9470794) genes. As a continuous variable, with a 1-point increase in the GRS or weighted (w) GRS, fasting plasma glucose (FPG) increased 0.045 and 0.044?mM, respectively (P?< 0.001 for both), after adjusting for confounders. Both GRS and wGRS showed an association with diabetes, with a multivariable-adjusted odds ratio (95% confidence interval) of 1.09 (1.00-1.19) and 1.12 (1.03-1.22), respectively, among all subjects. No significant associations were found between the GRS or wGRS and impaired fasting glucose or impaired glucose tolerance. CONCLUSIONS:The data suggest the association of 10 SNPs and the GRS or wGRS with diabetes risk. Genetic susceptibility to diabetes may synergistically affect the risk of diabetes in adulthood.

SUBMITTER: Song C

PROVIDER: S-EPMC6850447 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Effects of variants of 50 genes on diabetes risk among the Chinese population born in the early 1960s.

Song Chao C Wang Meng M Fang Hongyun H Gong Weiyan W Mao Deqian D Ding Caicui C Fu Qiqi Q Feng Ganyu G Chen Zheng Z Ma Yanning Y Yao Yecheng Y Liu Ailing A

Journal of diabetes 20190425 11

<h4>Background</h4>Genome-wide association studies have identified loci that significantly increase diabetes risk. This study explored the genetic susceptibility in relation to diabetes risk in adulthood among a Chinese population born in the early 1960s.<h4>Methods</h4>In all, 2129 subjects (833 males, 1296 females) were selected from the cross-sectional 2010 to 2012 China National Nutrition and Health Survey. Fifty diabetes-related single nucleotide polymorphisms (SNPs) were detected. Two diab ...[more]

PMID: 30907055

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Project description:The prevalence of obesity has been increasing sharply and has become a serious public health problem worldwide. Gene-environment interaction in obesity is a relatively new field, and little is known about it in Chinese adults. This study aimed to provide the effects of gene-environment interaction on obesity among Chinese adults. A stratified multistage cluster sampling method was conducted to recruit participants from 150 surveillance sites. Subjects born in 1960, 1961 and 1963 were selected. An exploratory factor analysis was used to classify the environmental factors. The interaction of single nucleotide polymorphisms (SNPs) and environmental factors on body mass index (BMI) and waist circumference were analyzed using a general linear model. A multiple logistic regression model combined with an additive model was performed to analyze the interaction between SNPs and environmental factors in obesity and central obesity. A total of 2216 subjects were included in the study (mean age, 49.7 years; male, 39.7%, female, 60.3%). Engaging in physical activity (PA) could reduce the effect of MC4R rs12970134 on BMI (? = -0.16kg/m2, p = 0.030), and also reduce the effect of TRHR rs7832552 and BCL2 rs12454712 on waist circumference (WC). Sedentary behaviors increased the effects of SNPs on BMI and WC, and simultaneously increased the effects of FTO rs9939609 and FTO rs8050136 on obesity and central obesity. A higher socioeconomic status aggravated the influence of SNPs (including FTO rs9939609, BNDF rs11030104, etc.) on BMI and WC, and aggravated the influence of SEC16B rs574367 on central obesity. The MC4R rs12970134 association with BMI and the FTO rs8050136 association with central obesity appeared to be more pronounced with higher energy intake (? = 0.140 kg/m2, p = 0.049; OR = 1.77, p = 0.004, respectively). Engaging in PA could reduce the effects of SNPs on BMI and WC; nevertheless, a higher socioeconomic status, higher dietary energy intake and sedentary behaviors accentuated the influences of SNPs on BMI, WC, obesity and central obesity. Preventative measures for obesity should consider addressing the gene-environment interaction.

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Effects of variants of 50 genes on diabetes risk among the Chinese population born in the early 1960s.

Publications

Effects of variants of 50 genes on diabetes risk among the Chinese population born in the early 1960s.

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