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Association of human leukocyte antigens-DQB2/DPA1/DPB1 polymorphism and pulmonary tuberculosis in the Chinese Uygur population.

ABSTRACT: BACKGROUND:Tuberculosis (TB) is the second-leading cause of death globally. Genetic polymorphisms in human leukocyte antigens (HLA)-DQB2, HLA-DPA1, and HLA-DPB1 may partly explain individual differences in TB susceptibility. METHODS:We performed a hospital-based case-control study to assess the genetic influence of single-nucleotide polymorphisms (SNPs) in the HLA (HLA-DPA, HLA-DPB, and HLA-DQB) on the development of TB. There were 248 TB-infected cases and 340 healthy controls in this study. RESULTS:The HLA-DQB2 rs7453920 genotype GG was applied as the reference group, the GA genotype was related to a considerably magnified risk of TB (GA vs. GG: adjusted OR = 1.547, 95% CI = 1.039-2.304, p = 0.032). Nevertheless, the other two SNPs were not associated with TB risk. Stratified analyses suggested that tobacco was associated with an increased risk of TB in HLA-DQB2 rs7453920 G>A. CONCLUSION:These results suggested that the functional HLA-DQB2 rs7453920 G>A polymorphism may contribute to the genetic susceptibility to TB. Nevertheless, the results were based on a limited sample size, and larger well-designed studies are expected to confirm these preliminary findings.

SUBMITTER: Wang X

PROVIDER: S-EPMC6418356 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Association of human leukocyte antigens-DQB2/DPA1/DPB1 polymorphism and pulmonary tuberculosis in the Chinese Uygur population.

Wang Xue X Cao Xudong X Zhang Wanjiang W Zhang Le L Lu Lijun L Li Xinyue X El-Ashram Saeed S Wu Jiangdong J Chen Chuangfu C

Molecular genetics & genomic medicine 20190101 3

<h4>Background</h4>Tuberculosis (TB) is the second-leading cause of death globally. Genetic polymorphisms in human leukocyte antigens (HLA)-DQB2, HLA-DPA1, and HLA-DPB1 may partly explain individual differences in TB susceptibility.<h4>Methods</h4>We performed a hospital-based case-control study to assess the genetic influence of single-nucleotide polymorphisms (SNPs) in the HLA (HLA-DPA, HLA-DPB, and HLA-DQB) on the development of TB. There were 248 TB-infected cases and 340 healthy controls in ...[more]

PMID: 30600606

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Project description:Tuberculosis (TB) is an infectious disease caused by a mycobacterial infection, with high morbidity and mortality worldwide. The pathogenesis of TB is still unclear; however, a growing body of evidence suggests that host genetic factors may play important roles in susceptibility to TB, and different gene polymorphisms in different ethnic and genetic backgrounds may lead to different effects. In view of the above theories, our research group used bioinformatics to screen for 12 single nucleotide polymorphisms (SNPs), including rs1045481, rs1045491, rs2740349, rs10719, rs642321, rs3744741, rs7813, rs3742330, rs3757, rs14035, rs720012, and rs4961280, which are derived from 6 main genes (i.e., GEMIN4, DICER1, DROSHA, DGCR8, AGO2, and RAN) acting in the microRNA-machinery pathway. We then analyzed the correlations between TB patients of Uygur in Xinjiang China and the above SNPs using a case-control study. The results showed that the genotypic distributions of rs720012 (from gene DGCR8) and rs4961280 (from gene AGO2) were not in accordance with the Hardy-Weinberg equilibrium (P?<?.05), so they were deleted. Subjects carrying the rs3742330 AG/GG genotype, rs1045481 GA genotype, rs1045491 CT genotype, and rs7813 AG genotype, respectively, had an increased risk of TB than individuals carrying rs3742330 AA genotype, rs1045481 GG/AA genotype, rs1045491 CC/TT genotype, and rs7813 AA/GG genotype between different groups. Expression quantitative trait loci analysis found that rs3744741 and rs2740349 from gene GEMIN4 had a regulatory effect, while rs3742330 from gene DICER1 had a reverse regulatory effect. Finally, according to the results of Linkage Disequilibrium between SNPs, the haplotype analysis showed that the haplotype of GCTAC from gene GEMIN4 had statistical differences when compared with active and inactive TB. The current experimental results provide a direction for our future research, and the research team will conduct more in-depth studies on the correlation between miRNA and TB.

Dataset Information

Association of human leukocyte antigens-DQB2/DPA1/DPB1 polymorphism and pulmonary tuberculosis in the Chinese Uygur population.

Publications

Association of human leukocyte antigens-DQB2/DPA1/DPB1 polymorphism and pulmonary tuberculosis in the Chinese Uygur population.

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