Zhang Xiuqin, Liu Reng-Yun, Lei Zhe, Zhu Yehan, Huang Jian-An, Jiang Xiefang, Liu Zeyi, Liu Xia, Peng Xiaobei, Hu Huacheng, Zhang Hong-Tao
Department of Respiratory Medicine, The First Affiliated Hospital, Medical College of Soochow University, Suzhou, PR China.
Int J Mol Med. 2009 Apr;23(4):485-93. doi: 10.3892/ijmm_00000155.
Obesity and inflammation are known to correlate with the pathogenesis of obstructive sleep apnea syndrome (OSAS). Interleukin (IL)-6, an important regulator of obesity and inflammation, was reported to phenotypically increase in patients with OSAS. This study aimed to investigate whether genetic variants in IL-6 confer susceptibility to OSAS. The study population consisted of 151 patients with OSAS and 75 healthy controls from Southeast China. Five haplotype-tagging single nucleotide polymorphisms (tSNPs) were selected across 21 kb of the IL-6 locus using Haploview software V4.1. The tSNPs were amplified by polymerase chain reaction (PCR) and genotyped by restriction enzyme digestion followed by gel electrophoresis. Linkage disequilibrium (LD) and haplotype reconstruction were carried out by means of a SHEsis program. No distribution difference of any of the five tSNPs between OSAS patients and controls was observed. However, in non-obese individuals (n=117), the minor allele G (rs1800796) decreased risk of OSAS compared with the major allele C [odds ratio (OR), 0.48; 95% confidence interval (CI), 0.26-0.86; p=0.014], and the haplotype TG (rs1880242, rs1800796) conferred a significantly decreased risk of OSAS than single allele G (rs1800796) (OR, 0.39; 95% CI, 0.20-0.74; p=0.003). Moreover, the severity of sleep-disordered breathing (measured by apnea hypopnea index) increased linearly in carriers of the C variant of IL-6 -572G/C polymorphism (14.3+/-5.1, 22.0+/-3.6 and 34.8+/-3.5 for GG, CG and CC, respectively; p=0.012). To the best of our knowledge, this is the first study to suggest that genetic variants in IL-6 could modify OSAS susceptibility. SNP genotyping of IL-6 is a potential strategy for detecting the risk of breathing disordered diseases in non-obese individuals.
众所周知，肥胖和炎症与阻塞性睡眠呼吸暂停综合征（OSAS）的发病机制相关。白细胞介素（IL）-6是肥胖和炎症的重要调节因子，据报道，OSAS患者的IL-6表型增加。本研究旨在调查IL-6基因变异是否会增加患OSAS的易感性。研究人群包括来自中国东南部的151例OSAS患者和75名健康对照者。使用Haploview软件V4.1在IL-6基因座的21 kb区域内选择了五个标签单核苷酸多态性（tSNP）。通过聚合酶链反应（PCR）扩增tSNP，并通过限制性内切酶消化和凝胶电泳进行基因分型。通过SHEsis程序进行连锁不平衡（LD）和单倍型重建。未观察到OSAS患者和对照组之间五个tSNP中的任何一个的分布差异。然而，在非肥胖个体（n = 117）中，与主要等位基因C相比，次要等位基因G（rs1800796）降低了患OSAS的风险[比值比（OR），0.48；95%置信区间（CI），0.26 - 0.86；p = 0.014]，并且单倍型TG（rs1880242，rs1800796）比单等位基因G（rs1800796）降低OSAS风险的幅度更大（OR，0.39；95% CI，0.20 - 0.74；p = 0.003）。此外，IL-6 -572G/C多态性的C变体携带者的睡眠呼吸紊乱严重程度（通过呼吸暂停低通气指数测量）呈线性增加（GG、CG和CC分别为14.3±5.1、22.0±3.6和34.8±3.5；p = 0.012）。据我们所知，这是第一项表明IL-6基因变异可能会改变OSAS易感性的研究。IL-6的SNP基因分型是检测非肥胖个体呼吸紊乱疾病风险的潜在策略。
