Effects of variants of 50 genes on diabetes risk among the Chinese population born in the early 1960s. Issue 11 (25th April 2019)

• Record Type: Journal Article
• Authors: Song, Chao; Wang, Meng; Fang, Hongyun; Gong, Weiyan; Mao, Deqian; Ding, Caicui; Fu, Qiqi; Feng, Ganyu; Chen, Zheng; Ma, Yanning; Yao, Yecheng; Liu, Ailing
• Is Part Of: Journal of diabetes. Volume 11:Issue 11(2019)
• Page Start: 857
• Page End: 868
• Publication Date: 2019-04-25
• Subjects: diabetes -- genetic susceptibility -- single nucleotide polymorphism; 糖尿病 -- 基因易感性 -- 单核苷酸多态性; Diabetes -- Periodicals; 618.3646005
• DOI: 10.1111/1753-0407.12922
• Languages: English
• ISSNs: 1753-0393

Abstract

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. Abstract : Highlights Ten single nucleotide polymorphisms were found to be associated with diabetes risk. There were significant associations of diabetes genetic risk scores and weighted diabetes genetic risk scores with fasting plasma glucose and diabetes. 摘要: 背景: 全基因关联性分析研究发现了能显著增加糖尿病发病风险的位点。本研究旨在探讨20世纪60年代初出生的中国人群糖尿病相关基因与糖尿病发病风险的关系。 方法: 从2010‐2012年中国居民营养与健康状况监测的研究对象中选取2129名在20世纪60年代初出生的中国人群作为研究对象，其中男性833名，女性1296名。对研究对象进行50个糖尿病相关的单核苷酸多态性(single nucleotide polymorphism，SNP)进行检测。然后用糖尿病相关变异计算得到两种糖尿病基因评分(GRS/weighted GRS)，分析其与糖尿病发病风险的关系。 结果: 研究发现MTNR1B (rs10830963)、KLHDC5 (rs10842994)、GRK5 (rs10886471)、CDKAL1 (rs10946398)、AP3S2 (rs2028299)、DGKB/TMEM195 (rs2191349)、 SCAP (rs4858889)、ANK1 (rs516946)、RASGRP1 (rs7403531)、 ZFAND3 (rs9470794)与糖尿病发病风险之间存在相关性。糖尿病基因评分作为连续变量时，校正混杂因素后，糖尿病基因评分(GRS)和加权GRS(wGRS)每增加一个单位，空腹血糖浓度分别增加0.045 mmol/L和0.044 mmol/L(两者均为 P <0.001)。GRS和wGRS均与糖尿病患病风险有关(分别为OR=1.09，95% CI: 1.00‐1.19；OR=1.12，95% CI: 1.03‐1.22)。未发现GRS及wGRS与空腹血糖异常和葡萄糖耐量受损发生相关。 结论: 研究发现10个SNP以及GRS或wGRS与糖尿病发病风险相关。糖尿病基因易感性会协同影响成年糖尿病的发病风险。