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.
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。.
Keywords: diabetes; genetic susceptibility; single nucleotide polymorphism; 单核苷酸多态性; 基因易感性; 糖尿病.
© 2019 National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention. Journal of Diabetes published by John Wiley & Sons Australia, Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.