CD14 -159 C>T gene polymorphism with increased risk of tuberculosis: evidence from a meta-analysis.

M Y Areeshi,Aditya K Panda,Shekhar C Bisht,Raju K Mandal,Shafiul Haque

doi:10.1371/journal.pone.0064747

Abstract

Cluster of differentiation 14 (CD14) gene is an important component of the human innate immune system and its role in tuberculosis (TB) has been sparsely documented. The enhanced plasma CD14 levels in TB patients as compared to healthy controls are associated with CD14 gene promoter (C-159T) polymorphism. In the past few years, the relationship between CD14 −159 C>T (rs2569190) polymorphism and risk of TB has been reported in various ethnic populations; however, those studies have yielded contradictory results. In this study systemic assessment was done for the published studies based on the association between CD14 −159 C>T polymorphism and TB risk retrieved from PubMed (Medline) and EMBASE search. A total number of 1389 TB cases and 1421 controls were included in this study and meta-analysis was performed to elucidate the association between CD14 −159 C>T polymorphism and its susceptibility towards TB. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for allele contrast, homozygous comparison, heterozygous comparison, dominant and recessive genetic model. It was found that T allele carrier was significantly associated with increased TB risk (T vs. C: p-value = 0.023; OR = 1.305, 95% CI = 1.038 to 1.640). Similarly, homozygous mutant TT genotype also revealed 1.6 fold increased risk of TB (TT vs. CC; p-value = 0.040; OR = 1.652, 95% CI = 1.023 to 2.667). Additionally, dominant genetic model demonstrated increased risk of developing TB (TT vs. CC+CT: p-value = 0.006; OR = 1.585, 95% CI = 1.142 to 2.201). The study demonstrates that CD14 gene (−159 C>T) polymorphism contributes increased susceptibility for TB. Moreover, this meta-analysis also suggests for future larger studies with stratified case control population and biological characterization for validation studies.

Highlights

Tuberculosis (TB) is an infectious disease, remains a major public health concern and leading cause of morbidity and mortality across the globe
Inclusion and Exclusion Criteria In order to minimize heterogeneity and facilitate the appropriate interpretation and understanding of the findings, studies included in the current meta-analysis had to meet the following criteria: a) evaluation of Cluster of differentiation 14 (CD14) 2159 C.T polymorphism and TB risk, b) use of case-control design, c) recruitment of pathologically confirmed TB patients and TB free controls, d) have available genotype frequency in cases and controls, e) the articles must be published in English language
Studies based on investigation of the levels of CD14 mRNA or protein expression or review articles were excluded

Summary

Introduction

Tuberculosis (TB) is an infectious disease, remains a major public health concern and leading cause of morbidity and mortality across the globe. It is estimated that approximately one-third of the world’s population is infected with Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, among them only 10% develop clinical disease [2]. This has maintained interest in that there is an inter-individual heterogeneity in host susceptibility for TB. Soluble CD14 (sCD14) is present in the circulation and other body fluids, and its level increases in serum plasma during inflammation and other infectious diseases [9,10]. Similar is the case of TB, where increased level of CD14 has been reported in TB patients [11]

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