Unidad de Hipertensión, Servicio de Medicina Interna, Hospital Universitario de Valme, Carretera de Cádiz S/N., 41014 Seville, Spain.
Gene. 2013 May 25;521(1):150-4. doi: 10.1016/j.gene.2013.03.024. Epub 2013 Mar 21.
Obstructive sleep apnea (OSA) is a common disorder characterized by the reduction or complete cessation in airflow resulting from an obstruction of the upper airway. Several studies have observed an increased risk for cardiovascular morbidity and mortality among OSA patients. Metabolic syndrome (MetS), a cluster of cardiovascular risk factors characterized by the presence of insulin resistance, is often found in patients with OSA, but the complex interplay between these two syndromes is not well understood. In this study, we present the results of a genetic association analysis of 373 candidate SNPs for MetS selected in a previous genome wide association analysis (GWAS). The 384 selected SNPs were genotyped using the Illumina VeraCode Technology in 387 subjects retrospectively assessed at the Internal Medicine Unit of the "Virgen de Valme" University Hospital (Seville, Spain). In order to increase the power of this study and to validate our findings in an independent population, we used data from the Framingham Sleep Study which comprises 368 individuals. Only the rs11211631 polymorphism was associated with OSA in both populations, with an estimated OR=0.57 (0.42-0.79) in the joint analysis (p=7.21×10(-4)). This SNP was selected in the previous GWAS for MetS components using a digenic approach, but was not significant in the monogenic study. We have also identified two SNPs (rs2687855 and rs4299396) with a protective effect from OSA only in the subpopulation with abdominal obesity. As a whole, our study does not support the idea that OSA and MetS share major genetic determinants, although both syndromes share common epidemiological and clinical features.
阻塞性睡眠呼吸暂停（OSA）是一种常见的疾病，其特征是上呼吸道阻塞导致气流减少或完全停止。多项研究观察到 OSA 患者心血管发病率和死亡率增加。代谢综合征（MetS）是一组心血管危险因素，其特征是存在胰岛素抵抗，常发生于 OSA 患者中，但这两种综合征之间的复杂相互作用尚不清楚。在这项研究中，我们报告了先前全基因组关联分析（GWAS）中选择的 373 个 MetS 候选 SNP 的遗传关联分析结果。使用 Illumina VeraCode 技术在 387 名回顾性评估的内科单位“Virgen de Valme”大学医院（西班牙塞维利亚）患者中对 384 个选择的 SNP 进行基因分型。为了提高这项研究的效力并在独立人群中验证我们的发现，我们使用了Framingham 睡眠研究的数据，该研究包含 368 个人。只有 rs11211631 多态性在两个群体中与 OSA 相关，联合分析中估计的 OR=0.57（0.42-0.79）（p=7.21×10(-4)）。该 SNP 在前代谢综合征 GWAS 中使用双基因方法选择，但在单基因研究中不显著。我们还鉴定了两个 SNP（rs2687855 和 rs4299396），它们仅在腹部肥胖亚群中具有保护作用，可预防 OSA。总的来说，我们的研究不支持 OSA 和 MetS 共享主要遗传决定因素的观点，尽管这两种综合征具有共同的流行病学和临床特征。
