The Uyghur population and genetic susceptibility to type 2 diabetes: potential role for variants in CAPN 10 , APM 1 and FUT 6 genes

• Published in: Journal of cellular and molecular medicine 2016-11, Vol.20 (11), p.2138-2147
• Main Authors: Zhao, Feifei, Mamatyusupu, Dolikun, Wang, Youxin, Fang, Honghong, Wang, Hao, Gao, Qing, Dong, Hao, Ge, Siqi, Yu, Xinwei, Zhang, Jie, Wu, Lijuan, Song, Manshu, Wang, Wei
• Format: Article
• Language: English
• Subjects: Bioindicators; Biomarkers; Body weight; Calpain; Cholesterol; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Disease; Gene loci; Genes; Genetic diversity; Genetic variance; Genomes; Glycosylation; Health risks; Insulin resistance; Metabolic syndrome; Minority & ethnic groups; Obesity; Overweight; Population; Population genetics; Risk factors; Single-nucleotide polymorphism; Studies
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12911

Genome‐wide association studies have successfully identified over 70 loci associated with the risk of type 2 diabetes mellitus (T2 DM ) in multiple populations of European ancestry. However, the risk attributable to an individual variant is modest and does not yet provide convincing evidence for clinical utility. Association between these established genetic variants and T2 DM in general populations is hitherto understudied in the isolated populations, such as the Uyghurs, resident in Hetian, far southern Xinjiang Uyghur Autonomous Region , China. In this case–control study, we genotyped 13 single‐nucleotide polymorphisms ( SNP s) at 10 genes associated with diabetes in 130 cases with T2 DM and 135 healthy controls of Uyghur, a Chinese minority ethnic group. Three of the 13 SNP s demonstrated significant association with T2 DM in the Uyghur population. There were significant differences between the T2 DM patients and controls in the risk allele distributions of rs3792267 ( CAPN 10 ) ( P = 0.002), rs1501299 ( APM 1 ) ( P = 0.017), and rs3760776 ( FUT 6 ) ( P = 0.031). Allelic carriers of rs3792267‐A, rs1501299‐T, and rs3760776‐T had a 2.24‐fold [ OR (95% CI ): 1.35–3.71], 0.59‐fold [ OR (95% CI ): 0.39–0.91], 0.57‐fold [ OR (95% CI ): 0.34–0.95] increased risk for T2 DM respectively. We further confirmed that the cumulative risk allelic scores calculated from the 13 susceptibility loci for T2 DM differed significantly between the T2 DM patients and controls ( P = 0.001), and the effect of obesity/overweight on T2 DM was only observed in the subjects with a combined risk allelic score under a value of 17. This study observed that the SNP s rs3792267 in CAPN 10 , rs1501299 in APM 1 , and rs3760776 in FUT 6 might serve as potential susceptible biomarkers for T2 DM in Uyghurs. The cumulative risk allelic scores of multiple loci with modest individual effects are also significant risk factors in Uyghurs for T2 DM , particularly among non‐obese individuals. This is the first investigation having observed/found genetic variations on genetic loci functionally linked with glycosylation associated with the risk of T2 DM in a Uyghur population.