CDKAL1、CDKN2A/2B、FTO基因多态性与维吾尔族2型糖尿病的关联以及基因间交互作用研究

摘要

目的 研究基因CDKALI、CDKN2A/2B、FTO的单核苷酸多态性(SNPs)与维吾尔族2型糖尿病的关联以及基因间的交互作用.方法 通过病例-对照研究的方法,收集新疆医科大学第一附属医院(以下简称“我院”)2012年3月～2013年9月期间住院的维吾尔族2型糖尿病患者1000例作为病例组,选择同期在我院进行体检的维吾尔族非糖尿病者1010例作为对照组.采用Sequenom MassARRAY(R)SNP技术检测CDKAL1、CDKN2A/2B 、FTO基因的7个SNPs位点,最终纳入研究的是所有位点均检测成功的病例组879例和对照组895例.两组各SNPs的基因型及等位基因频率的比较采用X2检验.使用Logistic回归分析各SNPs的遗传模型.使用GMDR 0.9软件分析各基因间交互作用.结果 7个位点的基因型分布均符合Hardy-Weinberg平衡(P＞0.05).位点rs10811661、rs7195539、rs8050136、rs9939609的基因型和位点rs8050136、rs9939609的等位基因分布在两组间分布差异有统计学意义(P＜0.05),两位点的风险等位基因均是A.两组间位点rs10811661、rs8050136、rs9939609的基因型分布在遗传模型中差异有统计学意义(P＜0.05).通过GMDR软件进行基因-基因交互作用分析,二阶交互作用模型rs10811661-rs7195539为最佳模型,进行1000次置换检验后P=0.014.结论 CDKAL1的基因多态性可能与维吾尔族2型糖尿病的发病风险无关.CDKN2A/2B (rs 10811661)、FTO (rs7195539、rs8050136、rs9939609)的基因多态性可能与维吾尔族2型糖尿病的发病风险有关,其中,rs8050136和rs9939609的等位基因A可能是维吾尔族2型糖尿病发病的风险等位基因.在维吾尔族2型糖尿病发病过程中CDKN2A/2B (rs 10811661)与FTO(rs7195539)间可能存在交互作用.%Objective To investigate the relationship among single nucleotide polymorphisms of CDKAL1,CDKN2A/ 2B,FTO,and type 2 diabetes mellitus (T2DM) in Uygur,and further to analyze the possible gene-gene interaction.Methods A case-control study was designed.1000 cases of hospitalized Uygur with T2DM were selected as cases group in the First Affiliated Hospital of Xinjiang Medical University from March 2012 to September 2013.1010 Uygur without diabetes mellitus (DM) who did physical examination during the same time in the same hospital were selected as the control group.Seven SNPs in CDKAL1,CDKN2A/2B and FTO were tested using the technology of Sequenom MassARRAY (R) SNP.Finally the cases,in which all the loci were successfully detected,were 879 in cases group and 895 in control group.Chi-square was used to analyze the distribution of genotype and allele.Logistic regression analysis was used to analyze the genetic models.Gene-gene interaction was analyzed by Generalized Multifactor Dimensionality Reduction 0.9 software.Results The genotype distributions of the 7 loci were in accordance with Hardy-Weinberg equilibrium （P ＞ 0.05).Genotype distributions of rs 10811661,rs7195539,rs8050136,rs9939609 and allele frequencies of rs8050136,rs9939609 were significantly different between eases group and control group (all P ＜ 0.05).The risk allele was A in loci rs8050136 and rs9939609.The genotype distributions of rs10811661,rs8050136,and rs9939609 differed significantly in genetic models (P ＜ 0.05).In the GMDR analysis,the second-order interaction of rs10811661-rs7195539 was the best model,after the 1000 times replacement tests,P=0.014.Conclusion The gene polymorphism in CDKAL1 may be unrelated with T2DM.The polymorphisms in CDKN2A/2B (rs10811661) and FTO (rs7195539,rs8050136,rs9939609) may be associated with T2DM,and A allele of rs8050136 and rs9939609 are likely risk alleles for T2DM in Uygur.There is potential interaction among CDKN2A/2B (rs10811661)-FTO (rs7195539) in the pathogenesis of T2DM in Uygur population.