【摘要】 目的 探讨肥胖相关基因多态性与阻塞性睡眠呼吸暂停低通气综合征(OSAHS)易感性关系。方法 联合基因-表型数据库(PHGKB)及在大量文献复习及既往研究基础上，筛选了与肥胖相关的17个为候选基因，在重度OSAHS组(n=50)与非OSAHS组(n=50)中行全部外显子以及侧翼序列进行高通量二代测序，最后选取有意义的位点进行基因型分析并计算基因频率，分析其与OSAHS易感性的关系，再利用在线平台，进行基因潜在互作图，进一步验证与OSAHS的关系。结果 对筛选出的基因行高通量二代测序，进行单因素Logistic回归分析，再调整混杂因素后，结果表明，PPARG基因rs12486170位点(OR=0.260,95%CI:0.079～0.852,P=0.026)和TNF基因rs1800630位点(OR=4.907,95%CI:1.112～21.666,P=0.036)分别是患OSAHS的保护因素和危险因素。与其余基因位点无相关性(P>0.05)。PPARG基因rs12486170 AA基因型比较，AG/GG基因型降低OSAHS的危险性(P=0.026)。此外，携带rs12486170 AG/GG基因型的受试者呼吸暂停指数(AHI)明显低于AA型(P=0.019)。TNF基因rs1800630携带A等位基因的受试者对OSAHS的风险显著增加(P=0.048),具有CA/AA基因型的个体OSAHS风险相对于CC基因型的个体显著增加(P=0.036),且AHI明显低于CC型(P=0.013)。笔者将筛选的与OSAHS关联强度最高的50个基因，进行基因潜在互作图计算拓扑特征。OSAHS有47个结节和484个边缘，最大连接值为43,越大的连接性值表明蛋白质之间有很强的相互作用，因此有助于稳定网络模型的关键性质，PPARG与TNF连接值分别为38与31,进一步证实与OSAHS的相关性。结论 笔者发现肥胖相关基因PPARG基因rs12486170位点、TNF基因rs1800630位点与OSAHS发病有关，分别是患OSAHS的保护因素和危险因素。更多还原

【Abstract】 Objective To explore the relationship between obesity-related gene polymorphism and susceptibility to obstructive sleep apnea hypopnea syndrome(OSAHS). Methods 17 Obesity-related genes were selected as candidate genes based on the combined gene-phenotype database(PHGKB) and a large number of literature review and previous studies and flanking sequences of obesity-related genes were sequenced in 50 cases(severe OSAHS group) and 50 cases(non-OSAHS group). Finally, significant loci were selected for genotype and allele frequency, and the relationship between allele frequency and OSAHS susceptibility was analyzed. Then the online platform was used to carry out the potential interaction group of gene to further verify the with OSAHS. Results We performed high-throughput second-generation sequencing on the selected genes, performed univariate Logistic regression analysis, and adjusted for confounding factors, the results showed that the PPARG gene rs12486170 varian(OR=0.260, 95% CI: 0.079-0.852, P=0.026) and TNF gene rs 1800630 varian(OR=3.342,95% CI:1.013-11.029, P=0.048) is the protective factors and risk factors of OSAHS.There was no correlation with other gene loci(P>0.05).PPARG gene rs12486170 AA genotype compared to the risk of obstructive sleep apnea(P=0.026). In addition, the respiratory suspension index(AHI) carrying the RS12486170 AG/GG genotype is significantly lower than the AA type(P=0.019).Compared with rs12486170 AA genotype of PPARG gene, AG/GG genotype reduced the risk of OSAHS.In addition, AHI of subjects with rs12486170 AG/GG genotype was significantly lower than that of AA genotype(P=0.019).TNF gene rs1800630 carrying A-allele subject significantly increased the risk of OSAHS(P=0.048), in addition to individual OSAHS risks with CA/AA genotypes, increased significantly with respect to CC genotypes(P=0.036) and AHI is significantly lower than the CC type(P=0.019).The maximum 50 genes associated with OSAHS were screened out for potential gene interaction mapping to calculate topological features.OSAHS has 47 nodules and 484 margins, and the maximum connection value is 43. A larger connection value indicates a strong interaction between proteins, thus helping to stabilize the key properties of the network model. The PPARG and TNF connection values are 38 and 31, respectively, further confirming the correlation between the OSAHS.Conclusion We found that obesity-related gene PPARG gene rs12486170 and TNF gene rs1800630 are associated with the pathogenesis of OSAHS, which are protective factors and risk factors for OSAHS.更多还原