Association between NRAMP1 gene polymorphism and multidrug-resistant tuberculosis in Han nationality of Yunnan

Abstract

Objective To explore the relationship between NRAMP1 gene 3´UTR single nucleotide polymorphism and MDR-resistant tuberculosis in Yunnan Han population, and to find out the influencing factors of NRAMP1 genotype.

Methods Polymorphism of NRAMP1 gene at 3´UTR was detected by PCR, the distribution and allele frequency difference of NRAMP1 gene 3´UTR genotypes were compared in the tuberculosis group (MDR-TB patients) and the control group (health examination population), and influencing factors of NRAMP1 genotype were analyzed by two-class logistic regression analysis of genotypes in tuberculosis group.

Results The distribution frequencies of TGTG+/+ at 3´UTR locus of NRAMP1 gene were 60.7%/71.3% in tuberculosis group ( n=300) and control group( n=300), respectively. The distribution frequencies of TGTG +/+- were 33.0%/24.7% in tuberculosis group and control group, respectively. The distribution frequencies of TGTG-/- were 6.3%/ 4.0% in tuberculosis group and control group, respectively (χ ²=7.779, P=0.020). The genotype TGTG +/- and allele TGTG- increased susceptibility to MDR-PTB ( OR: 1.573, 95% CI: 1.097-2.255; OR: 1.516, 95% CI: 1.136-2.022). In logistic regression analysis, compliance ( OR=3.919, 95% CI=1.071-14.343), adverse drug reactions ( OR=0.212, 95% CI=0.062-0.728) and tuberculous pleurisy ( OR=0.159, 95% CI=0.049-0.523)were the three factors influencing the allele TGTG-.

Conclusion TGTG - at 3´UTR locus of NRAMP1 gene is associated with MDR-PTB in Yunnan Han population. TGTG - is affected by compliance, adverse drug reactions and tuberculous pleurisy.

Abstract

摘要： 目的 探讨云南地区汉族人群 NRAMP1基因3´UTR位点单核苷酸多态性与耐多药肺结核发生的关系，并寻找基因型的影响因素。 方法应用聚合酶链式反应检测 NRAMP1基因3´UTR位点的多态性，比较感染组(耐多药肺结核患者)与对照组(健康体检人群)基因型的分布频率和等位基因的频率差异，并对感染组基因型的影响因素进行二分类logistic回归分析。 结果300例感染组与300例对照组 NRAMP1基因3´UTR位点的基因型TGTG+/+分布频率为60.7%/71.3%，基因型TGTG+/-分布频率为33.0%/24.7%，基因型TGTG-/-分布频率6.3%/4.0%，两组比较χ ²=7.779, P=0.020。基因型TGTG+/-增加了耐多药肺结核的易感性( OR:1.573,95% CI:1.097~2.255),等位基因TGTG-亦增加了其的易感性( OR:1.516,95% CI:1.136~2.022)。在影响因素分析中，患者的依从性( OR=3.919,95% CI=1.071~14.343)、药物的不良反应( OR=0.212,95% CI=0.062~0.728)、合并结核性胸膜炎( OR=0.159,95% CI=0.049~0.523)是等位基因TGTG缺失的影响因素。 结论云南汉族人群耐多药肺结核的发生与 NRAMP1基因3´UTR位点的TGTG缺失有关，而TGTG缺失又与患者的依从性、药物不良反应、合并结核性胸膜炎有关。