title: Gene Polymorphism Association with Type 2 Diabetes and Related Gene-Gene and Gene-Environment Interactions in a Uyghur Population.
abstract: BACKGROUND We investigated the association between 8 single-nucleotide polymorphisms (SNPs) at 3 genetic loci (CDKAL1, CDKN2A/2B and FTO) with type 2 diabetes (T2D) in a Uyghur population. MATERIAL AND METHODS A case-control study of 879 Uyghur patients with T2D and 895 non-diabetic Uyghur controls was conducted at the Hospital of Xinjiang Medical University between 2010 and 2013. Eight SNPs in CDKAL1, CDKN2A/2B and FTO were analyzed using Sequenom MassARRAY®SNP genotyping. Factors associated with T2D were assessed by logistic regression analyses. Gene-gene and gene-environment interactions were analyzed by generalized multifactor dimensionality reduction. RESULTS Genotype distributions of rs10811661 (CDKN2A/2B), rs7195539, rs8050136, and rs9939609 (FTO) and allele frequencies of rs8050136 and rs9939609 differed significantly between diabetes and control groups (all P<0.05). While rs10811661, rs8050136, and rs9939609 were eliminated after adjusting for covariates (P>0.05), rs7195539 distribution differed significantly in co-dominant and dominant models (P<0.05). In gene-gene interaction analysis, after adjusting for covariates the two-locus rs10811661-rs7195539 interaction model had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.5483 (P=0.014). In gene-environment interaction analysis, the 3-locus interaction model TG-HDL-family history of diabetes had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.7072 (P<0.001). The 4-locus interaction model, rs7195539-TG-HDL-family history of diabetes had a cross-validation consistency of 8/10 (P<0.001). CONCLUSIONS Polymorphisms in CDKN2A/2B and FTO, but not CDKAL1, may be associated with T2D, and alleles rs8050136 and rs9939609 are likely risk alleles for T2D in this population. There were potential interactions among CDKN2A/2B (rs10811661) - FTO (rs7195539) or FTO (rs7195539)-TG-HDL-family history of diabetes in the pathogenesis of T2D in a Uyghur population.
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Xinjiang Medical University, Urumchi , China (mainland).
authors.forename: Shan
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Xinjiang Medical University, Urumchi , China (mainland).
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Xinjiang Medical University, Urumchi , China (mainland).
authors.forename: Yong
authors.initials: Y
authors.lastname: Fan
authors.forename: Yinxia
authors.initials: Y
authors.lastname: Su
authors.forename: Qi
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital of Xinjiang Medical University, Urumchi , China (mainland).
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Hua
authors.initials: H
authors.lastname: Yao
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult; D012359:tRNA Methyltransferases / Q000235:genetics
chemical_list: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D012359:tRNA Methyltransferases; C525110:CDKAL1 protein, human