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

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（χ2=0.009，P =0.976；χ2=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（χ2=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(χ2= 0. 009,P = 0. 976;χ2 = 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 gene mutation occurred in 12 cases(63. 2% )among the 19 patients with family history of T2DM,the mutation rate of SLC22A1 gene was 77. 9% (162 / 208)in the 208 cases without family history of T2DM,the difference was not statistically significant( χ2 = 1. 367,P = 0. 242 ). Conclusion The mutation rate of rs34059508 and rs4646277 sites of SLC22A1 gene among Xinjiang Uygur men is 0. 4% and 5. 8% respectively. No effects of family history of T2DM are found on SLC22A1 gene mutation.