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

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.

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

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.