SLC11A1基因多态性与宁夏南部人群肺结核易感性研究

摘要

目的 探索SLC11A1基因rs17235409、rs17235416、rs3731865等位点多态性与中国宁夏回族自治区南部人群肺结核易感性的关系.方法 于2010年7-11月选取宁夏回族自治区南部的西吉、海原、泾原、彭阳、原州、同心、中卫、隆德等8个地区,并在该地区居住10年以上,且经当地疾病预防控制中心确诊为活动性肺结核的患者作为观察组,共965例.同期选取上述地区的健康人群作为对照组,共897名.收集研究对象基本信息,采集研究对象外周静脉血5 ml,应用乙二胺四乙酸(EDTA)抗凝,-80℃保存,用于提取基因组DNA.利用聚合酶链反应限制性片段长度多态性(PCR-RFLP)的方法对SLC11A1基因rs17235409、rs17235416、rs3731865位点进行基因分型,分析3个单核苷酸多态性(SNP)位点与结核易感性的关系.结果 rs17235409位点AA、AG、GG基因型在观察组和对照组中分布频率分别为1.4％(13/950)、23.5％(223/950)、75.1％(714/950)和2.7％ (23/842)、25.1％(211/842)、72.2％(608/842),两组比较差异无统计学意义(x2=5.12,P=0.077);rs17235416位点TGTG(-)/(-)、TGTG(+)/(-)、TGTG(+)/(+)基因型在观察组和对照组中的分布频率分别为1.8％(17/939)、22.7％(213/939)、75.5％(709/939)和3.4％(28/824)、23.8％(196/824)、72.8％(600/824),两组比较差异无统计学意义(x2=4.99,P=0.082);rs3731865位点CC、GC、GG基因型在观察组和对照组中分布频率分别为2.3％(22/951)、26.1％(248/951)、71.6％(681/951)和2.4％(20/843)、24.9％(210/843)、72.7％(613/843),两组比较差异无统计学意义(x2 =0.32,P=0.852).在隐性模型中,rs17235409位点AA、AG+ GG-基因型在观察组和对照组中分布频率分别为1.4％(13/950)、98.6％(937/950)和2.7％(23/842)、97.3％(819/842),两组分布频率比较差异有统计学意义(x2=4.21,P=0.040);但多因素logistic回归分析结果与单因素结果不-致,说明条件因素包括性别、年龄、民族等不同对结果有一定影响,所以不能说明rs17235409位点与肺结核发病相关(OR=0.51,95％CI=0.25～1.03,P=0.060).rs17235416位点TGTG(-)/(-)、TGTG(+)/(-)+TGTG(+)/(+)基因型在观察组和对照组中分布频率分别为1.8％(17/939)、98.2％(922/939)和3.4％(28/824)、96.6％(796/824),两组分布频率比较差异有统计学意义(x2 =4.45,P=0.038,OR=0.52、1.91,95％CI=0.23～0.97、1.04～3.51);经多因素logistic回归分析,排除性别、年龄和民族等条件因素对结果的影响,多因素结果与单因素结果相似,发现条件因素对结果无影响,结果仍有意义,说明携带rs17235416位点TGTG(+)/(-)和(或)TGTG(+)/(+)基因型的个体较携带TGTG(-)/(-)基因型的个体患肺结核的风险增加(OR=0.54,95％CI:0.29～1.00,P=0.049).结论 SLC11A1基因rs17235409和rs3731865位点多态性与宁夏南部地区人群肺结核易感性不相关.而rs17235416位点在隐性模型中,即携带TGTG(+)/(-)与TGTG(+)/(+)基因型的个体发病风险增高.%Objective To explore the relationship between the polymorphism of SLC11A1 gene (such as rs17235409,rs17235416 and rs3731865) and tuberculosis susceptibility in the population in the southern part of Ningxia Hui Autonomous Region.Methods Between July and November 2010,a total of 965 patients,who were from eight regions including Xiji,Haiyuan,Jingyuan,Pengyang,Yuanzhou,Tongxin,Zhongwei and Longde,in the southern part of Ningxia Hui Autonomous Region,had lived in these regions for more than 10 years and diagnosed with active tuberculosis by the local Centers for Disease Control and Prevention,were taken as case group.During the same period,a total of 897 healthy volunteers from the above regions were selected as control group.Their basic characteristics were collected.In addition,5 ml of peripheral venous blood was collected from the study subjects,followed by the addition of anticoagulant-ethylenediamine tetraacetic acid (EDTA),and then stored at -80 ℃ for the following extraction of genomic DNA.The genotyping of rs17235409,rs17235416 and rs3731865 in SLC11A1 gene was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),and then the relationship between three single nucleotide polymorphisms (SNPs) and tuberculosis susceptibility was analyzed.Results The distribution frequency of genotypes AA,AG,and GG at rs17235409 site in the case group was 1.4％ (13/950),23.5％ (223/950)and 75.1％ (714/950),respectively,while which was 2.7％ (23/842),25.1％ (211/842) and 72.2％ (608/842) in the control group,respectively;the difference was not statistically significant between two groups (x2=5.12,P=0.077).The distribution frequency of genotypes TGTG (-)/(-),TGTG (+)/(-) and TGTG (+)/(+) at rs17235416 site in the case group was 1.8％ (17/939),22.7％ (213/939) and 75.5％ (709/939),respectively,while which was 3.4％ (28/824),23.8％ (196/824) and 72.8％ (600/824) in the control group,respectively;there was no significant difference between two groups (x2=4.99,P=0.082).The distribution frequency of genotypes CC,GC and GG at rs3731865 site in the case group was 2.3％ (22/951),26.1％ (248/951) and 71.6％ (681/951),respectively,while which was 2.4 ％ (20/843),24.9％ (210/843) and 72.7％ (613/843) in the control group,respectively;the difference was not statistically significant (x2=0.32,P=0.852).In the recessive genetic model,the distribution frequency of genotypes AA and AG+GG at rs17235409 site in the case group was 1.4％ (13/950) and 98.6％ (937/950),respectively,while which was 2.7％ (23/842) and 97.3％ (819/842) in the control group,respectively;the difference was statistically significant (x2 =4.21,P=0.040).However,multivariable logistic regression analysis had inconsistent results with the univariate analyses,which indicated that the different condition factors,including genders,ages and ethnicity,had a certain effect on the results.Thus,these results did not explain that rs17235409 was related to the occurrence of tuberculosis (OR=0.51,95％CI=0.25-1.03,P=0.060).The distribution frequencies of genotypes TGTG (-)/(-) and TGTG (+)/(-)+TGTG (+)/(+) at rs17235416 site were 1.8％ (17/939) and 98.2％ (922/939) in the case group,while 3.4％ (28/824) and 96.6％ (796/824) in the control group,respectively;there was no significant difference between two groups (x2 =4.45,P=0.038,OR=0.52,1.91,95％CI=0.23-0.97 and 1.04-3.51,respectively).Based on multifactor logistic regression analysis adjusted to the condition factors,including gender,age and ethnicity,multifactor results were similar to single factor results,and condition factors were found to have no effects on the results,as well as the results were still significant (OR=0.54,95％CI=0.29 1.00,P=0.049),which indicated that the individuals with genotypes TGTG (+)/(-) and (or) TGTG (+)/(+) at rs17235416 site had increased risk of suffering from tuberculosis compared to individuals with genotypeTGTG (-)/(-) (OR=0.54,95％CI=0.29-1.00,P=0.049).Conclusion The polymorphisms of rs17235409 and rs3731865 in SLC11A1 gene were not correlated with tuberculosis susceptibility in the southern region of Ningxia.However,in the recessive genetic model,the onset risk of individuals with genotype TGTG (+)/(-) and TGTG (+)/(-) at rs17235416 site was increased.