Department of Otolaryngology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, China.
PLoS One. 2014 Jan 27;9(1):e86460. doi: 10.1371/journal.pone.0086460. eCollection 2014.
5-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.
Relevant 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.
Eight 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.
Our 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.
5-羟色胺受体（5-HTR）和 5-羟色胺转运体（5-HTT）基因多态性与阻塞性睡眠呼吸暂停综合征（OSAS）易感性有关。这些关联来自于零星的、不一致的、小样本量的研究，需要通过荟萃分析进一步评估。
通过搜索 PubMed、Embase、The Cochrane Library、中国知网（CNKI）、万方和维普，确定相关研究。从每个纳入的研究中提取合格数据。使用固定效应或随机效应模型计算比值比（ORs）。使用优势和隐性模型以及等位基因，ORs 和 95%置信区间（CI）来评估 5-羟色胺能基因多态性与 OSAS 之间的关联强度。Q 统计量用于评估同质性，Begg 检验用于评估发表偏倚。
最终纳入了 5-HTR2A 基因变异（包括 102T/C 和 1438G/A）、5-HTT 基因多态性（包括 5-HTT 基因启动子区（5-HTTLPR）和 5-羟色胺转运体内含子 2 可变数串联重复（STin2VNTR）与 OSAS 风险的相关性的 8 项研究的荟萃分析。5-HTR2A 1438G/A 的 G 等位基因、长 5-HTTLPR 和 10 个串联重复 STin2VNTR 显示增加 OSAS 易感性，OR 值分别为 2.33（A 对 G，95%CI 1.48-3.66）、1.24（L 对 S，95%CI：1.04-1.49）和 2.87（10 对 12，95%CI：1.38-5.97）。这些显著差异在显性和隐性模型中均有确定。在 5-HTR2A 1438G/A 基因多态性中，AA 基因型增加 OSAS 风险，在男性 OSAS 患者的隐性模型中 OR 为 4.21（95%CI：2.83-6.25），但在女性中未发现显著关联。
本荟萃分析表明，5-HTR2A 1438G/A 和 5-HTT 基因的多态性与 OSAS 的易感性有关。1438G/A 基因多态性的 A 等位基因主要分布在男性中，显著增加了 OSAS 的风险。
