NRAMP1基因3'UTR多态性与大理地区彝族肺结核易感相关性研究

目的 探讨NRAMP1基因3'UTR位点多态性与大理彝族肺结核病易感相关性及抗结核疗效的联系。方法 采用PCR - RFLP方法检测102例彝族肺结核病人及108例彝族健康人群的NRAMP1基因3'UTR位点的基因型，分析其与彝族人群患肺结核病的易感相关性，且对病人进行抗结核治疗1月后随访及不良反应观察，分析NRAMP1基因多态性与病人抗结核疗效的关系。结果 病例组中NRAMP1基因3'UTR位点AA基因型频率为20.59%，对照组中为5.55%，组间分布差异有统计学意义，χ2 = 14.135，P＜0.001。具有AA基因型的彝族患者肺结核的OR值为6.250，95% CI为2.404～16.247。抗结核治疗后，各基因型患者间胃肠道反应、肝损害及关节损害不良反应的发生率不同，突变型（GA + AA）患者比野生型（GG型）患者更易发生胃肠道反应、肝损伤、关节损害3种不良反应（P＜0.05）。需临床处理的较重不良反应在突变型（GA + AA）患者及野生型（GG型）患者中无统计学差异（P＞0.05）。结论 NRAMP1基因3'UTR位点多态性与大理彝族人群肺结核的易感性相关，可能是大理地区彝族人群肺结核易感的影响因素。A等位基因可能是大理彝族人群肺结核病发病危险因素（OR = 2.069，95% CI = 1.389～3.082 ）。患者抗结核治疗后发生的不良反应情况与NRAMP1基因3'UTR位点多态性存在相关性。

Study on the association of 3'UTR polymorphisms of NRAMP 1 gene with susceptibility to Pulmonary tuberculosis in Yi population of Dali

Objective To explore the correlation between the genetic polymorphism of NRAMP1 3'UTR with the susceptibility to tuberculosis of Yi population in Dali. Methods PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length) was conducted to analyze NRAMP1 3'UTR polymorphism of 102 TB-positive and 108 healthy people of Yi population living in Dali in order to study whether the gene polymorphism is correlated with the susceptibility to tuberculosis in Yi ethnicity. A follow-up study was also conducted after one-month treatment to analyze whether the resistance to treatment correlated with the gene polymorphism. Results The frequencies of NRAMP1 3'UTR AA genotypes in cases were 20.59%, and these figures were 5.55% in controls. The difference between the case and control had statistical significance (χ2=14.135, P<0.001). The OR of Yi population patients with NRAMP1 AA genotypes is 6.2504, and CI is 2.404-16.247. After anti-tuberculous treatment, the incidences of gastrointestinal reactions, liver damage and joint damage were different among patients with different genotypes. Mutant-type patients(GA+AA) are more likely to have the adverse reactions such as gastrointestinal reaction, liver injury and joint damage than those wild-type patients (GG) (P<0.05). There is no difference in severe adverse reactions requiring clinical treatment among mutant-type patients(GA+AA) and wild-type patients(GG). Conclusion The NRAMP1 3'UTR polymorphisms were possibly associated with susceptibility of tuberculosis in Yi population of Dali, which may be a influencing factor of susceptibility of tuberculosis in this group. NRAMP1 3'UTR A allele was possibly the risk factor of tuberculosis in Yi population of Dali(OR=2.069，95% CI=1.389-3.082). The side-effects of anti-tuberculous treatment correlated with the polymorphism.