A Serotonin Transporter Gene (SLC6A4) Polymorphism Is Associated with Reduced Risk of Irritable Bowel Syndrome in American and Asian Population: A Meta-Analysis

<div><p>Aim</p><p>Association studies of serotonin transporter gene SLC6A4 I/S polymorphism and irritable bowel syndrome (IBS) have shown inconsistent and contradictory results among different populations. In the present study, meta-analysis was performed to evaluate the association between SLC6A4 I/S polymorphism and IBS susceptibility.</p> <p>Methodology</p><p>Systemic assessment was performed for the published studies based on the association of SLC6A4 I/S polymorphism and IBS risk from PubMed (Medline), EMBASE search. A meta-analysis was done to appraise the said association. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model.</p> <p>Results</p><p>A total of twelve studies comprising 2068 IBS cases and 2076 controls were included in this meta-analysis. Overall, no significant results were obtained for S allele carrier (S vs. I: p=0.488; OR=1.073, 95% CI=0.879 to 1.311) Co-dominant (SS vs. II; p=0.587; OR=1.112, 95% CI=0.758 to 1.631), (IS vs. II; p=0.361; OR=0.878, 95% CI=0.665 to 1.160). Similarly, dominant (SS+IS vs. II: p=0.853; OR=0.974, 95% CI=0.736 to 1.288) and recessive (SS vs. II+IS: p=0.267; OR=1.172, 95% CI=0.886 to 1.522) genetic models did not demonstrate risk. In the subgroup population based analysis, reduced risks were found in American (IS vs. II: p=0.009; OR=0.685, 95% CI=0.516 to 0.908) and Asian (SS+IS vs. II; p=0.001; OR=0.116, 95% CI=0.068 to 0.197) population. However, no risk was observed in European population.</p> <p>Conclusions</p><p>This investigation clearly demonstrates that SLC6A4 (Ins/Del) polymorphism is associated with reduced risk of IBS in American and Asian population. However, future well-designed studies with stratified case control and biological characterization will be needed to validate this finding.</p> </div

Forest plot and ORs with 95% CI of CCL5 -403G>A polymorphism and TB risk (AA vs. GG).

<p>Forest plot and ORs with 95% CI of CCL5 -403G>A polymorphism and TB risk (AA vs. GG).</p

Forest plot for the association between IBS risk and the SLC6A4 (Ins/Del) polymorphism in Asian population (subgroup analysis).

<p>Forest plot for the association between IBS risk and the SLC6A4 (Ins/Del) polymorphism in Asian population (subgroup analysis).</p

A Meta-Analysis of the Association between the CC Chemokine Ligand 5 (CCL5) -403 G>A Gene Polymorphism and Tuberculosis Susceptibility

<div><p>Aim</p><p>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.</p><p>Methodology</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p></div

Main characteristics of all studies included in the meta-analysis.

<p>HB: Hospital based, PB: Population based.</p><p>ARMS PCR: Amplification Refractory Mutation System -Polymerase Chain Reaction.</p><p>PCR-RFLP: Restriction Fragment Length Polymorphism analysis of PCR amplified fragments.</p

Forest plot and ORs with 95% CI of CCL5 -403G>A polymorphism and TB risk (GA vs. GG).

<p>Forest plot and ORs with 95% CI of CCL5 -403G>A polymorphism and TB risk (GA vs. GG).</p

Genotypic distribution of CCL5 -403 G>A gene polymorphism included in the meta-analysis.

<p>Genotypic distribution of CCL5 -403 G>A gene polymorphism included in the meta-analysis.</p

Forest plot of overall IBS risk associated with SLC6A4 (Ins/Del) polymorphism.

<p>The squares and horizontal lines correspond to the study-specific OR and 95% CI.</p

Forest plot and ORs with 95% CI of CCL5 -403G>A polymorphism and TB risk (AA+GA vs. GG).

<p>Forest plot and ORs with 95% CI of CCL5 -403G>A polymorphism and TB risk (AA+GA vs. GG).</p

Forest plot and ORs with 95% CI of CCL5 -403G>A polymorphism and TB risk (AA vs. GG+GA).

<p>Forest plot and ORs with 95% CI of CCL5 -403G>A polymorphism and TB risk (AA vs. GG+GA).</p