中国汉族和维吾尔族MRC1基因多态性与肺结核病的相关性

Association study on MRC1 gene polymorphism with pulmonary tuberculosis in Chinese Han and Uygur populations

目的探讨中国汉族和维吾尔族人群MRC1基因多态性与肺结核病易感性的联系。方法应用PCR和DNA测序技术,对中国汉族454例和维吾尔族595例人群的MRC1基因的第7号外显子6个SNPs(G1186A、G1195A、T1212C、C1221G、C1303T和C1323T)基因型及基因频率分布进行检测,并进行连锁不平衡分析。结果中国汉族人群中G1186A位点等位基因G型分布频率在肺结核病组和正常健康组之间存在显著差异(P=0.037;OR=0.76;95%CI:0.58～0.98);AG基因型在两组之间存在显著性差异(P<0.01;OR=0.57;95%CI:0.37～0.87)。在年龄和性别校正后,G1186A位点在显性(P<0.01;OR=0.59;95%CI:0.40～0.87)、超显性(P=0.045;OR=0.69;95%CI:0.47～0.99)和加性模式(P=0.041;OR=0.76;95%CI:0.59～0.99)时,与肺结核病存在显著相关性。在维吾尔族人群中G1186A位点的等位基因G的分布频率在两组之间的分布具有显著性差异(P=0.031;OR=1.29;95%CI:1.02～1.62);基因型分析发现AA基因型在两组之间也存在显著性差异(P=0.033;OR=1.64;95%CI:1.04～2.60);在年龄和性别校正后,G1186A位点在加性模式下与肺结核病存在相关性(P=0.033;OR=1.28;95%CI:1.02～1.61)。连锁不平衡分析发现,构建的单体型GGTCCT(P=0.032;OR=0.75;95%CI:0.57～0.97)和GGTCCC(P=0.044;OR=0.57;95%CI:0.33～0.99)与肺结核病存在显著的相关性。结论 MRC1基因G1186A位点与中国人群肺结核病相关。

Objective The present study is aimed to investigate potential association of SNPs in exon 7 of the MRC1 gene with pulmonary tuberculosis （TB） in Chinese Han and Kazak populations. Methods Six SNPs （Gl186A, G1195A, T1212C, C1221 G, C1303T and C1323T） of the MRC1 gene were genotyped using the PCR and DNA sequencing methods in 454 Chinese Han and 595 Uygur subjects. Linkage disequilibrium analysis was performed to determine any linkage between the polymorphic sites. Results In a Chinese Han population, we found that the allele frequency of G1186A had a significant difference in frequency distribution between the two groups （P = 0. 037; OR = 0. 76; 95% CI, 0. 55-0. 98）. The AG genotypes were significantly correlated with pulmonary TB （P 〈0.01 ; OR =0. 57; 95% CI, 0.37 - 0.87）. After adjustment for age and gender, Gl186A site was found to be dominant （P 〈 0. 01; OR = 0. 59; 95% CI, 0. 40 -0. 87）, over-dominant （P =0. 045 ; OR =0. 69; 95% CI, 0. 47 -0. 99） and additive models （P =0. 041 ; OR = 0. 76; 95% CI, 0. 59 -0. 99） in association with pulmonary TB. In the Chinese Uygur population, we found that the allele frequency of G1186A was a significant difference between the two groups （ P = 0. 031 ; OR = 1.29 ; 95% CI = 1.02 - 1.62）. The AA genotype was significantly correlated with pulmonary TB （P = 0. 033; OR = 1.64; 95% CI = 1.04 - 2.60）. After adjustment for age and gender, G1186A site was found to be additive models （P = 0. 033 ; OR = 1.28; 95 % CI = 1.02 - 1.61 ） in association with pulmonary TB. By calculating the pairwise LD between 6 SNPs in the Chinese Uygur population, we found that the frequency of the haplotype GGTCCT （P =0. 032; OR =0. 75; 95% CI =0. 57 -0. 97） and GGTCCC （P = 0.044; OR = 0.57; 95% CI = 0.33 -0.99） was significantly associated with pulmonary TB. No association was found between the other 5 SNPs and TB （P 〉 0.05） in the Chinese population. Conclusion This study reports that genetic variants in the MRC1 gene may be associated with pulmonary TB in a Chinese population.