Identification of Novel Genetic Polymorphisms Associated with Type 2 Diabetes Mellitus: A Chinese Sib-Pair Study.

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.