A Meta-analysis of MBL2 Polymorphisms and Tuberculosis Risk.

Mohammed Y Areeshi,Shafiul Haque,Naseem Akhter,Mohtashim Lohani,Sajad A Dar,Raju K Mandal,Harishankar Mahto,Aditya K Panda,Mohd Wahid,Arshad Jawed

doi:10.1038/srep35728

Abstract

MBL2 gene encodes mannose-binding lectin, is a member of innate immune system. Earlier studies revealed that MBL2 gene variants, rs1800451, rs1800450, rs5030737, rs7096206, rs11003125 and rs7095891 are associated with impaired serum level and susceptibility to TB, but their results are inconsistent. A meta-analysis was performed by including 22 studies (7095 TB-patients and 7662 controls) and data were analyzed with respect to associations between alleles, genotypes and minor allele carriers to evaluate the potential association between MBL2 polymorphisms and TB risk. Statistically significant results were found only for the homozygous variant genotype (CC vs. AA: p = 0.045; OR = 0.834, 95% CI = 0.699 to 0.996) of rs1800451 and showed reduced risk of TB in overall population. However, other genetic models of rs1800450, rs5030737, rs7096206, rs11003125, rs7095891 and combined rs1800450, rs1800451, rs5030737 polymorphisms of MBL2 gene did not reveal any association with TB risk. Stratified analysis by ethnicity showed decreased risk of TB in African population for rs1800450 and rs1800451. Whereas, no association was observed between other MBL2 polymorphisms and TB risk in all the evaluated ethnic populations. In conclusion, MBL2 rs1800450 and rs1800451 polymorphisms play a protective role in TB infection and reinforce their critical significance as a potential genetic marker for TB resistance.

Highlights

Tuberculosis (TB) is essentially caused by Mycobacterium tuberculosis (M. tuberculosis) and still a major chronic infectious disease in most parts of the world
The preliminary search of PubMed (Medline), EMBASE and Google Scholar web-databases resulted 52 articles using the selected key words as mentioned in the methods section, and after detailed evaluation of the titles and abstracts, and after eliminating the duplicates, 27 articles dealing with evaluation of the association of MBL2 polymorphisms and TB risk were screened
Studies pertaining to protein expression or MBL2 mRNA levels or relevant review articles were omitted from this meta-analysis

Summary

Introduction

Tuberculosis (TB) is essentially caused by Mycobacterium tuberculosis (M. tuberculosis) and still a major chronic infectious disease in most parts of the world. It is assumed that susceptibility and progression to active TB is partly regulated by the host genetic factors[3], and this view is consistent with the findings of TB animal models[4] In these infected individuals, the chances of active disease development are based on the immune system’s ability to avert the multiplication of dormant M. tuberculosis[5]. The chances of active disease development are based on the immune system’s ability to avert the multiplication of dormant M. tuberculosis[5] In this regard, the identification of host genes and genetic variations would lead to a better understanding of the pathogenesis of TB and perhaps lead to novel strategies of the treatment or prophylaxis. Up to 1000 fold variations in MBL concentration level have been noticed in different individuals possibly because of deviating actions caused due to the combination of structural genes and promoter polymorphisms[10]

Methods

Results

Conclusion