汉族成年人 45 个标签单核苷酸多态性与 2 型糖尿病关联的前瞻性队列研究。
Investigation of the Association between 45 Tag SNPs and Type 2 Diabetes Mellitus in Han Chinese Adults: A Prospective Cohort Study.
机构信息
School of Public Health, Key Laboratory of Public Health Safety, NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, China.
Deqing County Center for Disease Prevention and Control, Deqing County, China.
出版信息
Public Health Genomics. 2021;24(3-4):123-130. doi: 10.1159/000513891. Epub 2021 Mar 11.
INTRODUCTION
The objective of this study was to examine the association between type 2 diabetes mellitus (T2DM) and genes identified in previous genome-wide association studies (GWASs) in rural Han Chinese adults.
METHODS
This prospective study included 1,832 adults aged ≥18 years in Deqing without diabetes at baseline. The subjects were followed up for 8.7 years on average. We selected 45 susceptible tag single-nucleotide polymorphisms (SNPs) for T2DM that have been identified in GWASs and genotyped. A Cox model was constructed to calculate the adjusted hazard ratios (aHRs) for the association between SNPs and incident T2DM.
RESULTS
The incidence rate of T2DM was 12.0 per 1,000 person-years. After adjustment for covariates and a Bonferroni correction, rs17584499 of protein tyrosine phosphatase, receptor-type D (PTPRD), rs11257655 and rs10906115 of cell division cycle 123 gene (CDC123), and rs12970134 of melanocortin-4 receptor (MC4R) were significantly associated with incident T2DM. The aHRs for incident T2DM were 1.75 (95% confidence interval [CI]: 1.28-2.40) and 1.61 (95% CI: 1.27-2.04) in association with an increasing number of T alleles in rs17584499 and rs11257655 under an additive genetic model, and the aHR was 1.72 (95% CI: 1.33-2.22) with an increasing number of A alleles in rs10906115. The aHRs under the dominant model were 1.82 (95% CI: 1.25-2.66) for TT + CT versus CC of rs17584499 and 2.04 (95% CI: 1.47-2.86) for AA + AG versus GG of rs10966115. The aHRs under the recessive model were 2.99 (95% CI: 1.30-6.89) for TT versus CT + CC of rs17584499, 1.92 (95% CI: 1.39-2.70) for TT versus CT + CC of rs11257655, and 2.54 (95% CI:1.22-5.29) for AA versus AG + GG of rs12970134. In addition, an increased incidence of T2DM was significantly associated with the TA haplotype of rs11257655 and rs10906115 (aHR = 1.81, 95% CI: 1.12-2.92), while a decreased incidence was associated with the CG haplotype (aHR = 0.49, 95% CI: 0.35-0.68) and the CT haplotype of rs1111875 and rs5015480 (aHR = 0.61, 95% CI: 0.37-0.98).
CONCLUSION
Variants of the PTPRD, CDC123, and MC4R genes were associated with the T2DM incidence in a rural Han Chinese population.
介绍
本研究旨在探讨先前全基因组关联研究（GWAS）中确定的 2 型糖尿病（T2DM）相关基因与农村汉族成年人的关系。
方法
本前瞻性研究纳入了德庆县基线时无糖尿病的 1832 名年龄≥18 岁的成年人。平均随访 8.7 年。我们选择了 45 个已确定的与 T2DM 相关的易感标签单核苷酸多态性（SNP）进行 GWAS 并进行基因分型。构建 Cox 模型计算 SNP 与新发 T2DM 之间的关联的调整后风险比（aHR）。
结果
T2DM 的发病率为每 1000 人年 12.0 例。在调整了协变量和 Bonferroni 校正后，蛋白酪氨酸磷酸酶受体型 D（PTPRD）的 rs17584499、细胞分裂周期 123 基因（CDC123）的 rs11257655 和 rs10906115 以及黑素皮质素-4 受体（MC4R）的 rs12970134 与新发 T2DM 显著相关。在加性遗传模型中，rs17584499 和 rs11257655 中 T 等位基因数量增加与新发 T2DM 相关的 aHR 分别为 1.75（95%置信区间 [CI]：1.28-2.40）和 1.61（95% CI：1.27-2.04），rs10906115 中 A 等位基因数量增加的 aHR 为 1.72（95% CI：1.33-2.22）。在显性模型中，rs17584499 的 TT + CT 与 CC 的 aHR 为 1.82（95% CI：1.25-2.66），rs10966115 的 AA + AG 与 GG 的 aHR 为 2.04（95% CI：1.47-2.86）。在隐性模型中，rs17584499 的 TT 与 CT + CC 的 aHR 为 2.99（95% CI：1.30-6.89），rs11257655 的 TT 与 CT + CC 的 aHR 为 1.92（95% CI：1.39-2.70），rs12970134 的 AA 与 AG + GG 的 aHR 为 2.54（95% CI：1.22-5.29）。此外，rs11257655 和 rs10906115 的 TA 单倍型与 T2DM 发生率的显著增加相关（aHR = 1.81，95% CI：1.12-2.92），而 CG 单倍型（aHR = 0.49，95% CI：0.35-0.68）和 rs1111875 和 rs5015480 的 CT 单倍型（aHR = 0.61，95% CI：0.37-0.98）与 T2DM 发生率的显著降低相关。
结论
PTPRD、CDC123 和 MC4R 基因的变异与农村汉族人群的 T2DM 发病率相关。
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