A meta-analysis of the association between the CC chemokine ligand 5 (CCL5) -403 G>A gene polymorphism and tuberculosis susceptibility

PLoS One. 2013 Aug 28;8(8):e72139. doi: 10.1371/journal.pone.0072139. eCollection 2013.

Abstract

Aim: Many case-control studies have been performed in the recent past to investigate the association between CCL5 -403 G>A (rs2107538) gene polymorphism and tuberculosis (TB) susceptibility in various ethnic groups. However, these studies have produced inconsistent and contradictory results. In the present study, meta-analysis was performed to assess the association between CCL5 -403 G>A polymorphism and TB risk.

Methodology: Quantitative synthesis was done for the published studies based upon association between CCL5 -403 G>A polymorphism and TB risk from PubMed (Medline), EMBASE web search. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic models.

Results: A total of six studies comprising 1638 confirmed TB cases and 1519 healthy controls were included in this meta-analysis. Variant A allele (A vs. G: p = 0.035; OR = 1.301, 95% CI = 1.019 to 1.662) and variant homozygous (AA vs. GG; p = 0.001; OR = 1.520, 95% CI = 1.202 to 1.923) carriers were significantly associated with TB susceptibility. Similarly, recessive model (AA vs. GG+GA: p = 0.016; OR = 1.791, 95% CI = 1.117 to 2.873) also indicated increased TB risk. Whereas, heterozygous (GA vs. GG: p = 0.837; OR = 1.028, 95% CI = 0.791 to 1.335) and dominant (AA+GA vs. GG: p = 0.222; OR = 1.188, 95% CI = 0.901 to 1.567) models failed to show increased risk of developing TB.

Conclusions: This meta-analysis suggests that there is a significant association between the CCL5 -403 G>A polymorphism and increased risk of TB. However, larger well-designed epidemiological studies with stratified case control and biological characterization may be helpful to validate this association.

Publication types

  • Meta-Analysis

MeSH terms

  • Case-Control Studies
  • Chemokine CCL5 / genetics*
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Models, Genetic
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Tuberculosis, Pulmonary / genetics*

Substances

  • CCL5 protein, human
  • Chemokine CCL5

Grants and funding

The authors have no support or funding to report.