Association between serotonin transporter (SERT) gene polymorphism and idiopathic pulmonary arterial hypertension: a meta-analysis and review of the literature

Abstract

Objective: Idiopathic pulmonary arterial hypertension (IPAH) is a rare and often fatal disease of unknown etiology. Serotonin transporter (SERT) protein, whose genes can have two allelic forms, namely long (L) and short (S), is suspected to be related to IPAH risk. Several studies have investigated the association between SERT's different allelic forms and IPAH but showed conflicting results. A meta-analysis of published studies was performed to allow a more reliable estimate of this association.

Methods: Relevant databases were searched to identify eligible studies published from 2000 to 2013. Odds ratios (OR) and 95% confidence intervals (CI) were determined for the gene-disease association using fixed or random effects models.

Results: A total of 6 studies with 451 IPAH subjects and 664 controls were included in this meta-analysis. A significant difference was found in the comparison between IPAH subjects and controls with LL vs. SS genotypes, and the pooled odds ratio (OR) with the fixed effects model was 1.446 (95% CI=1.036-2.018, p=0.030, I(2)=38.8%). However, no statistically significant differences were observed for LL vs. LS or LL vs. LS+SS. The pooled OR indicated no significant differences in IPAH risk between carriers of SERT L and S alleles (ORL VS. S=1.327, 95% CI=0.933-1.886, p=0.115).

Conclusion: This meta-analysis provides evidence suggesting an association between the SERT L/S polymorphism and IPAH. Individuals with the LL genotype have an obviously higher risk of developing IPAH than those with the SS genotype.

Keywords: 95% CI; 95% confidence interval; IPAH; Idiopathic pulmonary arterial hypertension; Meta-analysis; OR; PAH; PASMC; Polymorphism; SERT; Serotonin transporter; idiopathic pulmonary arterial hypertension; mPAP; mean pulmonary arterial pressure; odds ratio; pulmonary arterial hypertension; pulmonary artery smooth muscle cell; serotonin transporter.