5-HTT, BMPR2, EDN1, ENG, KCNA5 gene polymorphisms and susceptibility to pulmonary arterial hypertension: A meta-analysis

• Published in: Gene 2019-01, Vol.680, p.34-42
• Main Authors: Jiao, Yu-rui, Wang, Wei, Lei, Peng-cheng, Jia, Hui-ping, Dong, Jie, Gou, Yun-qian, Chen, Cheng-long, Cao, Jie, Wang, Ya-feng, Zhu, Yi-kun
• Format: Article
• Language: English
• Subjects: 5-HTT; BMPR2; EDN1; ENG; KCNA5; Meta-analysis; Pulmonary arterial hypertension
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2018.09.020

The influence of 5-HTT, BMPR2, EDN1, ENG, KCNA5 genes polymorphisms on susceptibility of pulmonary arterial hypertension remains uncertain. This meta-analysis is conducted for further study. We conducted a literature search on PubMed and ISI web of science databases for searching relevant articles until November 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A total of 17 articles with 2631 PAH subjects and 5139 controls were included in the final meta-analysis. Statistical software Stata13.0 was used for data-analysis. A significant relationship was found between the 5-HTT L/S polymorphism and PAH in all the genetic models [LL vs. SS: OR = 1.60, 95% CI, 1.11–2.32; LS vs. SS: OR = 1.55, 95% CI, 1.10–2.21; (LS + LL) vs. SS: OR = 1.56, 95% CI, 1.13–2.17; L vs. S: OR = 1.32, 95% CI, 1.08–1.62]. There were also associations of the SERT L/S polymorphism with IPAH and PAH in COPD [IPAH L/S: OR = 1.26, 95% CI, 1.01–1.57; PAH in COPD L/S: OR = 1.42, 95% CI, 1.04–1.94]. In addition, the results showed a statistically significant association between EDN1 rs5370 polymorphism and the risk of PAH in all the genetic models [TT vs. GG: OR = 3.32, 95% CI, 1.30–8.51; TG vs. GG: OR = 2.68, 95% CI, 1.54–4.66; (TG + TT) vs. GG: OR = 2.82, 95% CI, 1.69–4.71; T vs. G: OR = 2.43, 95% CI, 1.60–3.68]. However, the significant association was not found between BMPR2 rs1061157, KCNA5 rs10744676, ENG rs3739817 polymorphisms and the risk of PAH (all p > 0.05). 5-HTT L/S polymorphism and END1 rs5370 polymorphism were correlated with significantly increased risk of PAH. Moreover, L allele in 5-HTT gene increased susceptibility to IPAH and PAH in COPD. •5-HTT L/S polymorphism and END1 rs5370 polymorphism were correlated with significantly increased risk of PAH.•L allele in 5-HTT gene increased susceptibility to IPAH and PAH in COPD.•SERT L/S polymorphism was associated to the IPAH and PAN in COPD.