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13 February 2016 : Clinical Research  

Gene Polymorphism Association with Type 2 Diabetes and Related Gene-Gene and Gene-Environment Interactions in a Uyghur Population

Shan XiaoBCDEF, Xiaoyun ZengBDE, Yong FanCDE, Yinxia SuBDF, Qi MaDEF, Jun ZhuAEG, Hua YaoABCDEF

DOI: 10.12659/MSM.895347

Med Sci Monit 2016; 22:474-487

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.

Keywords: Alleles, Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics, Asian Continental Ancestry Group - genetics, Case-Control Studies, China, Diabetes Mellitus, Type 2 - genetics, gene-environment interaction, Genes, p16, Genetic Predisposition to Disease, Genotype, Polymorphism, Single Nucleotide, Risk Factors, young adult, tRNA Methyltransferases - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750