新疆维吾尔族人群结核病易感基因的多态性分析

Study on susceptibility genes polymorphisim to tuberculosis in Uighurs of Xinjiang

目的探讨人类自然抵抗相关巨噬细胞蛋白(NRAMP1)基因和维生素D受体(VDR)基因与新疆维吾尔族人群结核病易感性的关联。方法采用病例对照研究方法,选取224例新疆维吾尔族活动性肺结核患者为病例组,225例新疆维吾尔族健康人为对照组,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测VDR基因VDR-TaqI T/C、FokI C/T位点和NRAMPI基因3'-UTR多态性位点基因型,采用χ2检验分析3个位点多态性与新疆维吾尔族结核病易感性的关联。结果①新疆维吾尔族病例组中,NRAMP1基因的3’-UTR位点TGTG/TGTG基因型159例(71.0%),TGTG/del基因型56例(25.0%),TGTGdel/del基因型9例(4.0%);正常对照TGTG/TGTG基因型则为185例(82.2%),TGTG/del基因型36例(16.0%),TGT-Gdel/del基因型4例(1.8%)。TGTG/del基因型携带者患结核病的危险性是TGTG/TGTG基因型携带者的1.810倍。TGTGdel等位基因组间分布差异有显著性(P<0.05)。②在病例组中FF、Ff与ff 3种基因型分别为81例(36.2%)、127例(56.7%)、16例(7.1%);对照组的相应基因型为91例(40.4%)、120例(53.3%)、14例(6.2%)。FokI位点FF、Ff和ff基因型组间分布差异无显著性;等位基因F和f组间分布差异无显著性(P>0.05)。病例组中TT、Tt、tt 3种基因型分别为154例(68.8%)、66例(29.5%)、4例(1.8%);对照组的相应基因型则为170例(75.6%)、50例(22.2%)、5例(2.2%)。TaqI位点TT、Tt和tt基因型组间分布差异无显著性(P>0.05),等位基因T和t组间分布差异无显著性(P>0.05)。D'=0.017,r 2=0.00,两位点不存在连锁不平衡。结论①TGTG/del基因型可能是新疆维吾尔族人群结核病易感基因型;TGTG缺失等位基因可能是新疆维吾尔族人群结核病易感基因。②VDR基因FokI与TaqI位点多态性与新疆维吾尔族人群结核病易感性无关联,FokI和TaqI两位点间不存在连锁不平衡。

【Objective】 To investigate the relationship between polymorphisms of the VDR gene and the NRAMP1 gene and the susceptibility of PTB in Chinese Uighurs.【Methods】 Using case-control study,Genotyping of the 3＇-UTR of NRAMP1 gene,FokI and TaqI of VDR gene was done by PCR-RFLP among 224 patients and 225 healthy contacts.Chi-square test was used to analyze the association between the three sites and tuberculosis.【Results】 In the tuberculosis patients,genotype TGTG/TGTG,TGTG/del,and TGTGdel/del were observed in 159,56 and 9 cases respectively,while the genotypes of the healthy controls were TGTG/TGTG in 185,TGTG/del in 36 and TGTGdel/del in 4 case.TGTG/del genotype had significant increased risk of tuberculosis（OR=1.810）,the allele frequencies of TGTGdel were statistic significances in tuberculosis group compared with control group（P 0.01）.The genotype FF,Ff,ff were observed in 81,127 and 16 cases among tuberculosis group while in 91,120 and 14 cases among control group.The frequencies of VDR-FokI FF,Ff and ff genotypes had no statistically significant difference between the case and the control group.The allele frequencies of F and f were not statistic significances in tuberculosis group compared with control group（P 0.05）.The genotype of TT were in 154 cases,Tt in 66 cases and tt in 4 cases among patients while TT in 170 cases,Tt in 50 cases and tt in 5 cases among controls.The frequencies of VDR-TaqI tt,Tt,TT genotypes had no statistically significant difference between the case and the control group.The allele frequencies of T and t were not statistic significances in tuberculosis group compared with control group（P 0.05）.D′=0.017,r 2=0.00,The two polymorphisms of VDR didn＇t show linkage disequilibrium.【Conclusion】 The Uighurs in Xinjiang carrying TGTG/del genotype was apt to suffer tuberculosis;The TGTG del allele may be a risk factor for the tuberculosis of Xinjiang Uighurs.No evidence supported that the FokI and TaqI polymorphisms were associated with TB in Uighurs of Xinjiang.The two polymorphisms didn＇t show linkage disequilibrium.