The association of 5-HT2A, 5-HTT, and LEPR polymorphisms with obstructive sleep apnea syndrome: a systematic review and meta-analysis

PLoS One. 2014 Apr 22;9(4):e95856. doi: 10.1371/journal.pone.0095856. eCollection 2014.

Abstract

Objective: A consensus has not been reached regarding the association of several different gene polymorphisms and susceptibility to obstructive sleep apnea syndrome (OSAS). We performed a meta-analysis to better evaluate the associations between 5-HT2A, 5-HTT, and LEPR polymorphisms, and OSAS.

Method: 5-HT2A, 5-HTT, and LEPR polymorphisms and OSAS were identified in PubMed and EMBASE. The pooled odd rates (ORs) with 95%CIs were estimated using a fixed-effect or random-effect models. The associations between these polymorphisms and OSAS risk were assessed using dominant, recessive and additive models.

Results: Twelve publications were included in this study. The -1438 "A" allele of 5-HT2A was identified as a candidate genetic risk factor for OSAS (OR: 2.33, 95%CI 1.49-3.66). Individuals carrying the -1438 "G" allele had a nearly 70% reduced risk of OSAS when compared with AA homozygotes (OR: 0.30, 95%CI 0.23-0.40). There was no significant association between 5-HT2A 102C/T and OSAS risk, using any model. The "S" allele of 5-HTTLPR conferred protection against OSAS (OR: 0.80, 95%CI 0.67-0.95), while the "10" allele of 5-HTTVNTR contributed to the risk of OSAS (OR: 2.08, 95%CI: 1.58-2.73). The "GG" genotype of LEPR was associated with a reduced risk of OSAS (OR: 0.39, 95%CI 0.17-0.88).

Conclusion: The meta-analysis demonstrated that 5-HTR-1438 "A" and 5-HTTVNTR "10" alleles were significantly associated with OSAS. The "S" allele of 5-HTTLPR and the "GG" genotype of LEPR conferred protection against OSAS. Further studies, such as Genome-Wide Association study (GWAS), should be conducted in a large cohort of OSAS patients to confirm our findings.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Case-Control Studies
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Polymorphism, Single Nucleotide
  • Receptor, Serotonin, 5-HT2A / genetics*
  • Receptors, Leptin / genetics*
  • Risk
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Sleep Apnea, Obstructive / genetics*

Substances

  • LEPR protein, human
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Leptin
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins

Grants and funding

This study was supported by two grants from the China National Natural Science Foundation Council (81001333 and 81072479). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.