Yin Qiongzhou, Sun Kexin, Xiang Xiao, Juan Juan, Cao Yaying, Song Jing, Yang Yanfen, Shi Moye, Tian Yaohua, Liu Kuo, Fang Kai, Li Jing, Tang Xun, Wu Yiqun, Qin Xueying, Wu Tao, Chen Dafang, Hu Yonghua
1 Department of Epidemiology and Biostatistics, School of Public Public Health, Peking University, Beijing, China.
2 Department of Epidemiology & Biostatistics, Capital Medical University, Beijing, China.
Genet Test Mol Biomarkers. 2019 Jul;23(7):435-441. doi: 10.1089/gtmb.2018.0149.
To discover possible relationships between single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM) and its risk factors. The present sib-pair study was conducted in a rural community of Beijing, China. SNPs rs2297630, rs1746048, and rs1801157 located within or nearby the gene were genotyped using the allele-specific polymerase chain reaction method. Haseman-Elston regression was used to investigate linkages between these SNPs and T2DM. A generalized estimating equation logistic regression model was used to discover associations between the SNPs, T2DM, and its risk factors. A total of 3171 participants were recruited, comprising 2277 sib pairs. After Bonferroni correction ( = 0.016), rs2297630 was found to be significantly linked to ( = 0.003) and associated with T2DM (AA vs. GG/GA: OR = 2.26, 95% CI: 1.31-3.88, = 0.003). There were interactions between rs2297630 and dyslipidemia ( < 0.001) and between rs1746048 and hypertension ( = 0.011). Compared to dyslipidemia-free subjects with rs2297630 GG/GA genotypes, dyslipidemia patients with rs2297630 AA had a higher risk of T2DM (OR = 4.15, 95% CI: 2.24-7.67, < 0.001). Compared to hypertension-free subjects with rs1746048 CC genotypes, hypertension-free subjects with rs1746048 CT/TT had a decreased risk of T2DM (OR = 0.77, 95% CI: 0.60-0.99, = 0.045). A novel linkage and association was found between rs2297630 and T2DM. Moreover, novel interactions were found between rs2297630 and dyslipidemia as well as rs1746048 and hypertension. These findings will help identify individuals at higher risk of developing T2DM.
探索单核苷酸多态性（SNP）与2型糖尿病（T2DM）及其危险因素之间的潜在关系。本同胞对研究在中国北京的一个农村社区开展。采用等位基因特异性聚合酶链反应方法对位于该基因内部或附近的SNP rs2297630、rs1746048和rs1801157进行基因分型。使用Haseman-Elston回归研究这些SNP与T2DM之间的连锁关系。采用广义估计方程逻辑回归模型来发现SNP、T2DM及其危险因素之间的关联。共招募了3171名参与者，包括2277对同胞。经过Bonferroni校正（α = 0.016）后，发现rs2297630与T2DM显著连锁（P = 0.003）并与之相关（AA与GG/GA相比：OR = 2.26，95%CI：1.31 - 3.88，P = 0.003）。rs2297630与血脂异常之间存在相互作用（P < 0.001），rs1746048与高血压之间存在相互作用（P = 0.011）。与rs2297630 GG/GA基因型的无血脂异常受试者相比，rs2297630 AA基因型的血脂异常患者患T2DM的风险更高（OR = 4.15，95%CI：2.24 - 7.67，P < 0.001）。与rs1746048 CC基因型的无高血压受试者相比，rs1746048 CT/TT基因型的无高血压受试者患T2DM的风险降低（OR = 0.77，95%CI：0.60 - 0.99，P = 0.045）。发现rs2297630与T2DM之间存在新的连锁和关联。此外，还发现rs2297630与血脂异常以及rs1746048与高血压之间存在新的相互作用。这些发现将有助于识别患T2DM风险较高的个体。
