Abstract
AimMany 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.MethodologyQuantitative 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.ResultsA 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.ConclusionsThis 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.
Highlights
Tuberculosis (TB) is one of the commonest infectious disease, and remains a major public health concern owing to spread epidemically in many parts of the world [1]
Variant A allele (A vs. G: p = 0.035; odds ratios (ORs) = 1.301, 95% confidence intervals (95% class intervals (CIs)) = 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
This meta-analysis suggests that there is a significant association between the CC Chemokine Ligand 5 (CCL5) -403 G.A polymorphism and increased risk of TB
Summary
Tuberculosis (TB) is one of the commonest infectious disease, and remains a major public health concern owing to spread epidemically in many parts of the world [1]. It is expected that nearly one-third of the world’s population is infected with M. tuberculosis infection, only 5–15% of people develop active TB disease during their lifetime [3]. This indicates that host genetic differences may contribute to TB infection. M. tuberculosis has the ability to survive within the host phagocytic cells, and the relation between the host and the bacteria may lead to tissue damage characterized by granuloma formation, tissue necrosis along with development of cavities and, lastly, spreading of the disease [6,7]. Genes encoding chemokines and their cognate receptors play a significant role in the inammatory response during TB infection [9]
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