新疆维吾尔族人群SLC22A1基因多态性频率分布及糖尿病家族史对其突变的影响研究  

Frequency Distribution of SLC22A1 Gene Polymorphism and Effects of Family History of Diabetes on Mutation in Xinjiang Uygur Population

作　　者：张莉[1] 占琼[2] 赵军[3] 李建光[4] 周源[1] 杨欢杰 王宁[5] 

机构地区：[1]新疆医科大学第一附属医院,新疆乌鲁木齐市830011 [2]新疆医科大学研究生学院研究生管理科,新疆乌鲁木齐市830011 [3]新疆医科大学第一附属医院药学部,新疆乌鲁木齐市830011 [4]新疆医科大学校医院,新疆乌鲁木齐市830011 [5]新疆医科大学第一附属医院干部病房内一科,新疆乌鲁木齐市830011

出　　处：《中国全科医学》2017年第5期569-573,共5页Chinese General Practice

基　　金：国家自然科学基金资助项目(81360510)

摘　　要：背景转运蛋白(OCT)是近年来备受关注的药物转运体,由SLC22A1基因编码。SLC22A1基因具有显著的遗传多态性,已在多个种族中发现了多个基因突变,是引起2型糖尿病(T2DM)患者二甲双胍生物利用度差异的重要原因。目的研究新疆维吾尔族青年男性SLC22A1基因rs34059508、rs4646277位点等位基因和基因型的频率分布,以及T2DM家族史对SLC22A1基因突变的影响,为T2DM患者基因导向性二甲双胍个体化治疗提供理论依据。方法2014年9月—2015年9月,招募新疆维吾尔族男性健康志愿者276例为研究对象。采集受试者外周血5 ml,提取DNA,采用Snapshot技术平台分析受试者SLC22A1基因rs34059508、rs4646277位点等位基因、基因型频率和基因突变情况。结果 SLC22A1基因rs34059508、rs4646277位点基因频率分布符合Hardy-Weinberg遗传平衡,具有群体代表性(χ~2=0.009,P=0.976;χ~2=0.246,P=0.620)。亚洲人群、高加索人群、非裔美国人群、新疆维吾尔族人群SLC22A1基因rs34059508位点等位基因及基因型频率比较,差异有统计学意义(P<0.05);其中,新疆维吾尔族人群SLC22A1基因rs34059508位点等位基因A频率低于高加索人群(P<0.001)。亚洲人群、汉族人群、新疆维吾尔族人群SLC22A1基因rs4646277位点等位基因及基因型频率比较,差异有统计学意义(P<0.05);其中,新疆维吾尔族人群SLC22A1基因rs4646277位点等位基因T频率高于汉族人群(P<0.017)。19例有T2DM家族史者中12例(63.2%)发生SLC22A1基因突变,208例无T2DM家族史者SLC22A1基因突变率为77.9%(162/208),差异无统计学意义(χ~2=1.367,P=0.242)。结论新疆维吾尔族男性SLC22A1基因rs34059508、rs4646277位点突变率分别为0.4%、5.8%;未发现T2DM家族史对SLC22A1基因突变产生影响。Background Transport protein is a drug transporter that has attracted much attention in recent years. It is encoded by SLC22A1 gene. SLC22A1 gene has significant genetic polymorphism, and its multiple mutations have been found in many races. It is an important cause of metformin bioavailability differences in patients with type 2 diabetes mellitus （T2DM）. Objective To study the frequency distribution of alleles and genotypes of rs34059508 and rs4646277 sites of SLC22A1 gene in Xinjiang Uygur young men, explorer the effects of family history of diabetes on mutation, and provide theoretical basis for individualized treatment of metformin with gene orientation of T2DM patients. Methods From September 2014 to September 2015, 276 Uygur male healthy volunteers in Xinjiang were recruited. The 5 ml peripheral blood was collected, and DNA were extracted. The alleles and genotypes of rs34059508 and rs4646277 sites of SLC22A1 gene and nutation among the subjects were analyzed by Snapshot technology platform. Results The frequency distribution of the alleles of rs34059508 and rs4646277 sites of SLC22A1 gene was consistent with the genetic equilibrium of Hardy -Weinberg, which presents group representativeness （x^2 = 0. 009, P = 0. 976 ; x^2 = 0. 246, P = 0. 620）. There were significant differences in the frequency of alleles and genotypes of rs34059508 sites of SLC22A1 gene in the Asian population, Caucasian population, African American population, Xinjiang Uygur population （ P 〈 0. 05 ） ; the frequency of allele A of rs34059508 sites of SLC22A1 gene in the Xinjiang Uygur population was lower than that of the Caucasian population （ P 〈 0. 001 ）. There were significant differences in the frequency of alleles and genotypes of rs4646277 sites of SLC22A1 gene in the Asian population, Han population, Xinjiang Uygur population （ P 〈 0. 05 ） ; the frequency of allele T of rs4646277 sites of SLC22A1 gene in the Xinjiang Uygur population was higher than that of the Han population （P 〈 0. 017）. SLC22A1

关 键 词：糖尿病 2型 生物利用度 SLC22A1基因 多态性 单核苷酸 维吾尔族 

分 类 号：R587.1[医药卫生—内分泌]