核苷酸结合寡聚化结构域2基因多态性与肺结核发病风险的关联  

Genetic polymorphisms of nucleotide binding oligomerization domain 2 gene and the risk of pulmonary tuberculosis

作　　者：潘洪秋[1] 陈永忠 王建明[1] 

机构地区：[1]南京医科大学公共卫生学院流行病与卫生统计学系,211166 [2]镇江市第三人民医院结核科

出　　处：《中华传染病杂志》2013年第7期408-412,共5页Chinese Journal of Infectious Diseases

基　　金：国家自然科学基金资助项目（81072351）;江苏省自然科学基金资助项目（BK2012694）;江苏省科技支撑计划资助项目（BE2011841）;科技部重大专项资助项目（2009ZX10004-904）;江苏省高校优势学科建设工程PAAD

摘　　要：目的在中国人群中验证核苷酸结合寡聚化结构域2（NOD2）基因多态性与结核病发病风险的关联性。方法选择1043例肺结核患者和808名健康对照开展验证性病例对照研究，所有对照均无肺结核和恶性肿瘤史，按性别和年龄与病例组进行频数匹配。采用TaqMan技术对外周静脉血提取的基因组DNA进行NOD2基因分型，检测位点包括rs3135499、rs7194886、rs8057341和rs9302752。计数资料用卡方检验，采用非条件Logistic回归模型计算比值比（OR）及其95％可信区间（CI）。结果以全部肺结核患者为病例组进行分析，检测的4个NOD2基因多态位点与肺结核发病风险无关联。痰培养阳性的肺结核患者rs7194886单核苷酸多态性（SNP）与结核病遗传易感性有关联，与CC基因型比较，携带cT／TT基因型的个体患结核病风险增高（OR—1．35，95％CI：1．05～1．72，P-0．018）；调整潜在的混杂因素后，携带cT／TT基因型的个体患结核病风险仍增高（OR-1．35，95％CI：1．05～1．73）。分层分析显示，rs7194886多态位点的效应（CT／TT基因型相对于TT基因型）在男性（OR-1．44，95％CI：1．08～1．92）、年龄〈55岁（OR—1．51，95％CI：1．05～2．16）、吸烟者（OR-1．53，95％CI：1．07～2．18）、饮酒者（OR-1．84，95％CI：1．01～3．33）差异具有统计学意义（均P〈0．05），但层间-致性检验P〉0．05。单倍型分析显示，rs9302752C—rs7194886T携带者罹患肺结核的风险上升（x2=4．27，P-0．039）。结论免疫相关基因NOD2多态位点rs7194886可能与中国人群肺结核病遗传易感性有关。Objective To validate the association between genetic polymorphisms of nucleotide binding oligomerization domain 2 （NOD2） gene and the risk of tuberculosis in Chinese population. Methods A validation case-control study was performed with a total of 1043 pulmonary tuberculosis patients and 808 healthy controls. All controls had no history of tuberculosis or malignancy, and were matched with cases by sex and age. Genomic DNA from the peripheral blood samples of participant was extracted. Single nueleoside polymorphisms （SNP） of rs3135499, rs7194886, rs8057341, and rs9302752 in the NOD2 gene were genotyped using a TaqMambased allelie discrimination system. The chi-square test was used to analyze categorical data and Logistic regression model was used to calculatethe odds ratio （OR） and 95% confidence interval （CI）. Results When all patients as the cases were included in the analysis, no significant association was found between the four SNP of NOD2 gene and the risk of pulmonary tuberculosis. In a subgroup analysis by restricting cases to sputum culture positive patients, the variant genotypes of rs7194886 were significantly associated with an altered risk of tuberculosis. Compared with the CC genotype, individuals carrying the CT/TT genotype of rs7194886 had an increased risk （OR =1. 35, 95%CI： 1. 05- 1. 72） for sputum culture positive tuberculosis. After adjusted for potential confounders, the increased risk of CT/TT genotype was still observed （OR= 1.35, 95%CI： 1.05--1. 73）. Stratification analysis revealed that the effect of the SNP rs7194886 （CT/TT vs TT） was significant among men （OR= 1. 44, 95%CI： 1.08 -- 1. 92）, individuals with age 〈55 years （OR=I. 51, 95%/oCI： 1.05--2.16）, smokers （OR=I. 53, 95%CI： 1.07--2.18）, and alcohol drinkers （OR= 1.84, 95%CI： 1.01--3.33）. But the heterogeneity test was not significant. Haplotype analysis showed that the rs9302752C-rs？194886T haplotype was associated with an increased risk of sputum culture positive tubercul

关 键 词：结核 肺 多态现象 遗传 核苷酸转运蛋白质类 疾病遗传易感性 

分 类 号：R521[医药卫生—内科学]