Association of the miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms with susceptibility to pulmonary tuberculosis in the Chinese Uygur, Kazak and Southern Han populations.

Xing Zhang,Zhongliang Chen,Zhifen Pan,Dandan Xu,Chong Wang,Changming Liu,Zhongjie Li,Xiang Li,Fang Wu,Yanyuan Li,Wanjiang Zhang,Jiyan Liu,Ji-Cheng Li,Tingting Jiang,Zepeng Ping

doi:10.1186/s12879-015-0771-9

Abstract

BackgroundSingle nucleotide polymorphisms (SNPs) within precursor microRNAs (miRNAs) can affect miRNAs expression, and may be involved in the pathogenesis of pulmonary tuberculosis (TB). This study aimed to investigate potential associations between the four precursor miRNA SNPs (miR-146a C > G, miR-149 T > C, miR-196a2 T > C, and miR-499 T > C) and susceptibility to pulmonary TB in the Chinese Uygur, Kazak, and Southern Han populations.MethodsA case-control study was performed on Chinese Uygur (n = 662), Kazak (n = 612), and Southern Han (n = 654) populations using the PCR-PFLR method. The allele and genotype frequencies for all populations were analyzed. Linkage disequilibrium was performed, and different models of inheritance were tested.ResultsThe allele and genotype frequencies of the miR-499 SNP were significantly different between the TB patients group and the healthy control group in the Uygur population, and were found to be codominant, dominant, recessive and additive models in association with pulmonary TB. The haplotype CTCC showed significant correlation with pulmonary TB. The allele and genotype frequencies of miR-146a and miR-196a2 SNPs were significantly different between the two groups in the Kazak population. The miR-146a SNP was found to be codominant, recessive and additive models, whereas, the miR-196a2 SNP was found to be codominant, dominant, and additive models in association with pulmonary TB. The haplotypes TCCC and CCCT showed significant correlation with pulmonary TB.ConclusionsThe results suggested that susceptibility to pulmonary TB may be closely related to individual differences caused by genetic factors among different ethnic groups in China.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0771-9) contains supplementary material, which is available to authorized users.

Highlights

Single nucleotide polymorphisms (SNPs) within precursor microRNAs can affect miRNAs expression, and may be involved in the pathogenesis of pulmonary tuberculosis (TB)
The present study is the first to report that miR-146a, miR-149, miR-196a2, and miR-499 single nucleotide polymorphisms (SNPs) can be associated with susceptibility to pulmonary TB in the Chinese Uygur, Kazak, and Southern Han populations
The frequency of CC genotype in the pulmonary TB group was lower than the control group, and there was a significant difference between the two groups (P = 0.001; odds ratios (OR) = 5.344; 95% confidence intervals (CI), 1.803-15.83)

Summary

Introduction

Single nucleotide polymorphisms (SNPs) within precursor microRNAs (miRNAs) can affect miRNAs expression, and may be involved in the pathogenesis of pulmonary tuberculosis (TB). This study aimed to investigate potential associations between the four precursor miRNA SNPs (miR-146a C > G, miR-149 T > C, miR-196a2 T > C, and miR-499 T > C) and susceptibility to pulmonary TB in the Chinese Uygur, Kazak, and Southern Han populations. Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a chronic disease that can present serious threats to human health. According to the World Health Organization (WHO) global TB report, an estimated 8.56 million of people developed active form of TB in 2012 and 1.26 million died from the disease (including 320 000 deaths among HIV-positive people). The prevalence rate of active, sputum smearpositive, and sputum culture-positive pulmonary TB in these populations have been found to be 464/10000, 160/10000, and 38/10000, respectively, and were 1.26, 1.51 and 3.88 times higher than the national average, respectively.

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