A Systematic Review and Meta-Analysis of the Association between Serotonergic Gene Polymorphisms and Obstructive Sleep Apnea Syndrome

Abstract

Background5-Hydroxytryptamine receptor (5-HTR) and 5-hydroxytryptamine transporter (5-HTT) gene polymorphisms have been reported to be associated with susceptibility to obstructive sleep apnea syndrome (OSAS). The associations, derived from sporadic, inconsistent, small-sample-size studies, need to be evaluated further in a meta-analysis.MethodsRelevant studies were identified by searching PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. Eligible data were extracted from each included study. Odds ratios (ORs) were calculated using a fixed-effects or a random-effects model. The ORs and 95% confidence interval (CI) were used to assess the strength of the association between serotonergic gene polymorphisms and OSAS in the dominant and recessive models, as well as alleles. The Q statistic was used to evaluate homogeneity and Begg’s test was used to assess publication bias.ResultsEight studies were finally included in the meta-analysis of the association between 5-HTR2A gene variants (including 102T/C and 1438G/A), 5-HTT gene polymorphisms (including 5-HTT gene-linked promoter region (5-HTTLRP), and serotonin transporter intron 2 variable number tandem repeat (STin2VNTR) and OSAS risk. The G allele of 5-HTR2A 1438G/A, long 5-HTTLPR, and 10-tandem-repeats STin2VNTR were shown to increase OSAS susceptibility, with ORs of 2.33 (A vs. G, 95% CI 1.48–3.66), 1.24 (L vs. S, 95% CI: 1.04–1.49), and 2.87 (10 vs. 12, 95% CI: 1.38–5.97), respectively. These significant differences were determined in both dominant and recessive models. Of the 5-HTR2A 1438G/A gene polymorphism, the AA genotype increased the OSAS risk, with an OR of 4.21 (95% CI: 2.83–6.25) in a recessive model in male OSAS patients, but no significant association was found in females.ConclusionsOur meta-analysis demonstrated that polymorphisms in the 5-HTR2A 1438G/A and 5-HTT genes contributed to susceptibility to OSAS. The A allele of the 1438G/A gene polymorphism is predominantly distributed in males and increased the OSAS risk significantly.

Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans

“…We also examined generalizability of previously reported AHI candidate gene results to our Hispanic/Latino cohorts (see Table E6) (23)(24)(25)(26)(27)(28)(29)(30)(31). Of 17 SNPs tested We searched for SNPs with supporting ENCODE or Roadmap Epigenomics regulatory evidence as calculated by HaploReg (33).…”

Obstructive sleep apnea syndrome susceptible genes in the Chinese population: a meta-analysis of 21 case–control studies

“…In this process, 5-HT reuptake is mediated by the 5-HT transporter (5-HTT). VNTR can affect enhancer function and transcription of the 5-HTT gene, and LPR can influence 5-HT [38][39][40], which may contribute to the susceptibility of OSAS.…”

5-HTR2A and IL-6 polymorphisms and obstructive sleep apnea-hypopnea syndrome

“…The polymorphism of the genes that code for 5-HTR alter its transcription, affecting the number of receptors in the serotoninergic system, and may increase the risk of OSAHS. Recently, 3 meta-analyses (6)(7)(8) revealed that no differences were observed in the prevalence of T102C (rs6311) polymorphisms in the case and control groups (P>0.05). However, the -1438G-A polymorphism in the 5-HTR2A gene was significantly correlated with the increased risk of OSAHS, showing that the 'T' and 'C' allele are not involved in OSAHS.…”