Association between 5-HT2A receptor polymorphisms and risk of obstructive sleep apnea and hypopnea syndrome: a systematic review and meta-analysis.

Obstructive sleep apnea and hypopnea syndrome (OSAHS) is a common disorder with several predisposing factors, which may include genetic causes. Studies of the association of susceptibility to and severity of OSAHS with the polymorphisms of the 5-HTR 2A/2C genes have had low statistical power and have yielded inconsistent results. To clarify the association we perform a meta-analysis that combines the genotyping data from all eligible published studies. We quantitatively analyzed five publications, which included a pool of 633 cases and 512 controls, addressing the 5-HT receptor polymorphism and the risk of OSAHS. Hardy-Weinberg equilibrium (HWE) and the minor allele frequency of genetic frequency distributions for the controls were calculated. Differences in the distribution of genotypes between cases and controls were compared by odds ratios (ORs) with their 95% confidence intervals (CIs). For each genetic model, data were pooled using fixed- or random-effects models, depending on the inter-publication heterogeneity. Our results from pooled data showed that individuals carrying the 5-HTR 2A -1438G/A AA genotype had an increased risk of OSAHS (OR=3.69, 95% CI=1.92-7.08) compared with those carrying the GG genotype. Significant results were also reached under a recessive model (OR=3.16, 95% CI=2.33-4.30, p<0.01). However, the results declined to an OR of 2.16 (95% CI=0.9-5.21) in a homozygote model when the studies were restricted to HWE. No statistically significant results concerning an association of the 102C/T polymorphism of the 5-HTR 2A gene with OSAHS were reached (p>0.05 for each genetic model). This meta-analysis suggested that the 5-HTR 2A -1438G/A genotype might modulate an elevated risk of OSAHS. No association of the 5-HTR 2A 102C/T genotype polymorphism with OSAHS was established. However, some publications exhibited HWE bias, which might influence the reliability of pooled data. Further studies in this field, using larger samples, better designs and additional ethnicities, are warranted. Crown