Association of Mannose-binding Lectin Polymorphisms with Tuberculosis Susceptibility among Chinese.

Cheng Liu,Wenjun Ding,Yanxiao Rong,Zongde Zhang,Li Zheng,Fengjiao Du,Dongxing Ma,Yuling Wang,Yujie Wei,Zhiqin Mei,Yuehua Zhu,Huiliang Liu,Tao He,Haibin Wang,Xueqiong Wu

doi:10.1038/srep36488

Abstract

Tuberculosis (TB) is caused by infection of Mycobacterium tuberculosis. Host genetic variability is an important determinant of the risk of developing TB in humans. Although the association between MBL2 polymorphisms and TB has been studied in various populations, the results are controversial. In this study four functional single-nucleotide polymorphisms (SNPs, H/L, X/Y, P/Q and A/B) across the MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chinese Han origin, consisting of 1,020 patients with pulmonary TB and 1,020 controls. We found that individuals carrying variant allele at A/B (namely BB or AB genotypes) was associated with increased susceptibility to TB (odds ratios [OR] = 1.57, 95% confidence interval [CI] 1.30–1.91, P = 1.3 × 10−6). Additionally, LYPB haplotype showed a significant association with increased risk of TB (OR = 1.54, 95% CI 1.27–1.87, P = 4.2 × 10−6; global haplotype association P = 3.5 × 10−5). Furthermore, individuals bearing low- or medium- MBL expression haplotype pairs had an increased risk of TB (OR = 1.56, 95% CI 1.29–1.90, P = 1.4 × 10−6). Thus, the reduced expression of functional MBL secondary to having MBL2 variants may partially mediate the increased susceptibility to TB risk.

Highlights

MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chinese Han origin, consisting of 1,020 patients with pulmonary TB and 1,020 controls
The four functional single-nucleotide polymorphisms (SNPs) in the MBL2 gene is in linkage disequilibrium (LD) and more appropriate to be investigated together
We investigated all of the four functional SNPs in the MBL2 gene, individually or in haplotype or haplotype pairs, in a large case-control population of Chinese Han origin, totally consisting of 1,020 patients with TB and 1,020 controls

Summary

Introduction

MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chinese Han origin, consisting of 1,020 patients with pulmonary TB and 1,020 controls. Six single-nucleotide polymorphisms (SNPs) in exon 1 (codon 52 A/D, codon 54 A/B, and codon 57 A/C) and in the promoter and 5′-untranslated regions (nt −550 H/L, nt −221 X/Y, and nt + 4 P/Q) of the MBL2 gene are associated with serum levels and/ or functions of MBL These genetic variations are associated with a wide variety of diseases, including respiratory tract infections[3,8,9,10,11]. Low levels of MBL (associated with variant alleles at the promoter and exon 1 regions of the MBL2 gene) were reported to protect against tuberculosis[12,13], supporting the hypothesis that MBL binding can enhance the uptake of intracellular pathogens by phagocytes, and promote infection[12,14]. Conflicting results are not unexpected in association studies for several reasons, including small sample size, marginal statistical significance, detection of genotypes, or ethnic heterogeneity

Methods

Results

Conclusion