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目的探讨人类自然抵抗相关巨噬细胞蛋白1(NRAMP1)基因INT4和3’UTR位点多态性与中国北方汉族成人肺结核发病的关系。方法采用1∶1配对的病例对照研究设计,用聚合酶链反应-限制性片段长度多态性分析方法检测NRAMP1基因中INT4和3’UTR两个多态性位点,对与肺结核相关的危险因素进行问卷调查,进行单因素和多因素条件logistic回归分析,同时对基因型与肺结核病变的性质和程度进行研究。结果对124对研究对象进行了INT4和3’UTR两个多态性位点的基因分型,3’UTRTGTG+/del基因型病例组频率显著高于对照组,粗OR值(95%CI)为2.923(1.557~5.487)。病例组和对照组INT4各基因型频率比较差异均无统计学意义。对17个环境危险因素进行了单因素分析,在多因素分析中调整卡痕、体重指数、人均居住面积、家族史4个因素后,3’UTRTGTG+/del基因型仍与肺结核显著相关,调整OR值(95%CI)为2.955(1.369~6.381)。在INT4不同基因型中,病例组和对照组肺结核病变性质差异具有统计学意义(χ2=9.634,P<0.05)。结论NRAMP1基因3’UTR位点多态性可能是中国北方汉族成人肺结核的易感因素,而INT4多态性可能与肺结核的病变性质有关系。
Objective To investigate the relationship between polymorphisms of INT4 and 3’UTR of human natural resistance associated macrophage 1 (NRAMP1) gene and the incidence of pulmonary tuberculosis in adults of northern Han China. Methods A 1: 1 paired case-control study was designed to detect polymorphisms of INT4 and 3’UTR in NRAMP1 gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The risk factors for tuberculosis Questionnaire survey was conducted, and single-factor and multi-factor conditional logistic regression analysis was conducted, and the nature and degree of genotype and pulmonary tuberculosis were also studied. Results The genotypes of two polymorphic sites of INT4 and 3’UTR were genotyped in 124 pairs of subjects. The frequency of 3’UTRTGTG + / del genotype group was significantly higher than that of the control group. The crude OR value (95% CI) was 2.923 (1.557 ~ 5.487). There was no significant difference in the frequencies of INT4 genotype between the case group and the control group. Univariate analysis of 17 environmental risk factors showed that the 3’UTRTGTG + / del genotype was still significantly associated with pulmonary tuberculosis after adjusting for signs of karmy, body mass index, per capita living space, and family history in multivariate analysis, adjusting for OR The value (95% CI) was 2.955 (1.369 ~ 6.381). Among the different genotypes of INT4, there were significant differences in the nature of tuberculosis in case group and control group (χ2 = 9.634, P <0.05). Conclusion The 3’UTR polymorphism of NRAMP1 gene may be a susceptible factor for adult pulmonary tuberculosis in Han nationality in northern China, whereas the polymorphism of INT4 may be related to the pathological changes of pulmonary tuberculosis.