title: The Uyghur population and genetic susceptibility to type 2 diabetes: potential role for variants in CDKAL1, JAZF1, and IGF1 genes.
abstract: Substantial evidence suggests that type 2 diabetes mellitus (T2DM) is a multi-factorial disease with a strong genetic component. A list of genetic susceptibility loci in populations of European and Asian ancestry has been established in the literature. Little is known on the inter-ethnic contribution of such established functional polymorphic variants. We performed a case-control study to explore the genetic susceptibility of 16 selected T2DM-related SNPs in a cohort of 102 Uyghur objects (51 cases and 51 controls). Three of the 16 SNPs showed significant association with T2DM in the Uyghur population. There were significant differences between the T2DM and control groups in frequencies of the risk allelic distributions of rs7754840 (CDKAL1) (p=0.014), rs864745 (JAZF1) (p=0.032), and rs35767 (IGF1) (p=0.044). Carriers of rs7754840-C, rs35767-A, and rs864745-C risk alleles had a 2.32-fold [OR (95% CI): 1.19-4.54], 2.06-fold [OR (95% CI): 1.02-4.17], 0.48-fold [OR (95% CI): 0.24-0.94] increased risk for T2DM, respectively. The cumulative risk allelic scores of these 16 SNPs differed significantly between the T2DM patients and the controls [17.1±8.1 vs. 15.4±7.3; OR (95%CI): 1.27(1.07-1.50), p=0.007]. This is the first study to evaluate genomic variation at 16 SNPs in respective T2DM candidate genes for the Uyghur population compared with other ethnic groups. The SNP rs7754840 in CDKAL1, rs864745 in JAZF1, and rs35767 in IGF1 might serve as potential susceptibility loci for T2DM in Uyghurs. We suggest a broader capture and study of the world populations, including who that are hitherto understudied, are essential for a comprehensive understanding of the genetic/genomic basis of T2DM.
authors.affiliation: 1 School of Public Health, Capital Medical University , Beijing, China .
authors.forename: Manshu
authors.initials: M
authors.lastname: Song
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhao
authors.forename: Longjin
authors.initials: L
authors.lastname: Ran
authors.forename: Mamatyusupu
authors.initials: M
authors.lastname: Dolikun
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wu
authors.forename: Siqi
authors.initials: S
authors.lastname: Ge
authors.forename: Hao
authors.initials: H
authors.lastname: Dong
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Zhai
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Yan
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.forename: Xinghua
authors.initials: X
authors.lastname: Yang
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Guo
authors.forename: Youxin
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D056970:Co-Repressor Proteins; D015331:Cohort Studies; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D012359:tRNA Methyltransferases
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C583557:IGF1 protein, human; C430460:JAZF1 protein, human; D009363:Neoplasm Proteins; D007334:Insulin-Like Growth Factor I; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human