白介素-1β基因多态性与睡眠呼吸暂停综合征的相关性

目的 探讨白介素-1β(IL-1β)基因多态性与睡眠呼吸暂停综合征的关系。方法 纳入2010年1至12月新疆维吾尔自治区人民医院高血压科住院且行多导睡眠监测的高血压患者850例,根据多导睡眠监测结果分为原发性高血压组(225例)和高血压合并睡眠呼吸暂停综合症(OSAS)组(625例)。首先在96例重度OSAS患者中测序筛查IL-1β基因功能区的变异位点,选取代表性变异位点,应用Taqman-PCR在研究人群中进行基因型鉴定并开展病例-对照关联研究。结果 在IL-1β基因的功能区共发现1个新的和5个已知的变异位点,选取3个代表性变异位点进行基因型鉴定。IL-1β基因rs1143633位点的等位基因频率在总人群及男性人群中分布差异有统计学意义(χ²=9.258,P=0.002;χ²=5.119,P=0.024);总人群、男性人群及女性人群中rs1143633变异不同基因型组间各项睡眠呼吸监测参数差异均无统计学意义(P＞0.05),但总人群及男性人群中CT基因型的呼吸暂停低通气指数值比CC、TT基因型高,而夜间最低血氧饱和度在3种基因型间(CC＞CT＞TT)有逐渐增高趋势。总人群、男性人群及女性人群中两组间单体型频率差异均无统计学意义(P均＞0.05)。Logistic回归分析显示在总人群及男性人群中IL-1β基因rs1143633变异位点CT基因型是OSAS的危险因素(OR=1.574,95%CI=1.061~2.437,P=0.042;OR=1.887,95%CI=1.091~3.265,P=0.023)。结论 IL-1β基因rs1143633变异位点可能与睡眠呼吸暂停综合征有关。

Association of Interleukin-1β Genetic Polymorphisms with Obstructive Sleep Apnea Syndrome

Objective To investigate the association between interleukin(IL)-1β genetic polymorphisms and obstructive sleep apnea syndrome(OSAS).Methods Totally 850 individuals with hypertension were included.All of them were checked by polysomnography in the Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region from January to December in 2010.According to the results of polysomnography,these subjects were divided into non-OSAS group(n=225)and OSAS group(n=625).Genetic variations were sequenced and screened at loci over functional region of IL-1β gene in 96 patients with severe OSAS.The typical loci were selected for genotyping by TaqMan-polymerase chain reaction in 850 subjects.Results One novel and 5 known variations in the IL-1β gene were identified,and then three representative mutation loci were selected for genotyping.The allele frequency distribution of rs1143633 was significantly different between the OSAS and non-OSAS groups in the total and male populations(χ²=9.258,P=0.002;χ²=5.119,P=0.024,respectively).Although the parameters of sleep apnea monitoring showed no significant difference in individuals with CC,CT,and TT genotypes of rs1143633 in total,male,and female populations(P＞0.05),the median of the apnea hypopnea index of CT genotype was significantly higher than that of CC and TT in total and male populations and the mean of the lowest blood oxygen saturation increased in individuals with CC,CT,and TT genotypes of rs1143633 in total and male populations.Haplotype was no significantly associated with OSAS in total,male,and female populations(P＞0.05).Logistic regression analysis showed that CT genotype of rs1143633 variation was a risk factor for OSAS in total and male populations(OR=1.574,95% CI=1.061-2.437,P=0.042;OR=1.887,95% CI=1.091- 3.265,P=0.023).Conclusion The rs1143633 polymorphism in IL-1β gene may be associated with OSAS.