title: The Uyghur population and genetic susceptibility to type 2 diabetes: potential role for variants in CAPN10, APM1 and FUT6 genes.
abstract: Genome-wide association studies have successfully identified over 70 loci associated with the risk of type 2 diabetes mellitus (T2DM) 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 T2DM 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 (SNPs) at 10 genes associated with diabetes in 130 cases with T2DM and 135 healthy controls of Uyghur, a Chinese minority ethnic group. Three of the 13 SNPs demonstrated significant association with T2DM in the Uyghur population. There were significant differences between the T2DM patients and controls in the risk allele distributions of rs3792267 (CAPN10) (P = 0.002), rs1501299 (APM1) (P = 0.017), and rs3760776 (FUT6) (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 T2DM respectively. We further confirmed that the cumulative risk allelic scores calculated from the 13 susceptibility loci for T2DM differed significantly between the T2DM patients and controls (P = 0.001), and the effect of obesity/overweight on T2DM was only observed in the subjects with a combined risk allelic score under a value of 17. This study observed that the SNPs rs3792267 in CAPN10, rs1501299 in APM1, and rs3760776 in FUT6 might serve as potential susceptible biomarkers for T2DM in Uyghurs. The cumulative risk allelic scores of multiple loci with modest individual effects are also significant risk factors in Uyghurs for T2DM, 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 T2DM in a Uyghur population.
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhao
authors.affiliation: College of the Life Sciences and Technology, Xinjiang University, Urumqi, China.
authors.forename: Dolikun
authors.initials: D
authors.lastname: Mamatyusupu
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
authors.forename: Honghong
authors.initials: H
authors.lastname: Fang
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Dong
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Ge
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Yu
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wu
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China. songms@ccmu.edu.cn.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China. songms@ccmu.edu.cn.
authors.forename: Manshu
authors.initials: M
authors.lastname: Song
authors.affiliation: School of Public Health, Capital Medical University, Beijing, China. wei.wang@ecu.edu.au.|Municipal Key Laboratory of Clinical Epidemiology, Beijing, China. wei.wang@ecu.edu.au.|School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia. wei.wang@ecu.edu.au.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002154:Calpain / Q000235:genetics*; D016022:Case-Control Studies; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D005647:Fucosyltransferases; C515956:FUT6 protein, human; D002154:Calpain; C415197:calpain 10
keywords: 
  APM1
  ; 
  CAPN10
  ; 
  FUT6
  ; Uyghur; susceptibility loci; type 2 diabetes