Fang Ming, Huang Yueye, Zhang Yuan, Ning Zhongping, Zhu Luoning, Li Xinming
Department of Cardiology, Hainan General Hospital, Haikou, Hainan, China; Department of Cardiology, Shanghai Zhoupu Hospital, Shanghai, China.
Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
J Am Soc Hypertens. 2017 Mar;11(3):171-177. doi: 10.1016/j.jash.2017.01.011. Epub 2017 Feb 3.
Interleukin 6 (IL-6) is a multifunctional proinflammatory cytokine that is elevated in patients with pulmonary arterial hypertension (PAH). Single nucleotide polymorphisms in the promoter region of IL-6 have been reported to transcriptional regulate the expression of IL-6. The aim of the present study is to investigate the roles of two common polymorphisms (-572C/G [rs1800796] and -6331T/C [rs10499563]) of IL-6 in idiopathic PAH (IPAH). A total of 338 IPAH patients and 352 age- and gender-matched healthy controls were enrolled. Genotyping of the two polymorphisms was performed by polymerase chain reaction and direct sequencing. Serum IL-6 levels were determined by ELISA assay. The frequencies of -572C/G genotypes CC, CG, and GG were found to be 63.6%, 32.3%, and 4.1% in IPAH patients group and 51.7%, 39.5%, and 8.8% in the controls, respectively. Compared with the individuals carrying the common genotype CC, the individuals carrying the GG genotype had a decreased risk of IPAH (adjusted odds ratio, 0.40; 95% confidence interval, 0.20-0.77; P = .006). The CG genotype and G allele carriers (CG/GG genotypes) were also observed to be associated with decreased risks of IPAH. Moreover, we found that individuals harboring -572GG or GC genotype showed significantly lower IL-6 levels than those harboring the -572CC genotype. No association between -6331T/C polymorphism and risk of IPAH or IL-6 levels was found. These results suggest that IL-6 promoter polymorphism -572C/G, but not -6331T/C, is associated with serum IL-6 levels and risk of IPAH.
白细胞介素6（IL-6）是一种多功能促炎细胞因子，在肺动脉高压（PAH）患者中水平升高。据报道，IL-6启动子区域的单核苷酸多态性可转录调节IL-6的表达。本研究旨在探讨IL-6的两个常见多态性位点（-572C/G [rs1800796]和-6331T/C [rs10499563]）在特发性PAH（IPAH）中的作用。共纳入338例IPAH患者和352例年龄及性别匹配的健康对照。通过聚合酶链反应和直接测序对这两个多态性位点进行基因分型。采用酶联免疫吸附测定法测定血清IL-6水平。在IPAH患者组中，-572C/G基因型CC、CG和GG的频率分别为63.6%、32.3%和4.1%，在对照组中分别为51.7%、39.5%和8.8%。与携带常见基因型CC的个体相比，携带GG基因型的个体患IPAH的风险降低（校正比值比，0.40；95%置信区间，0.20 - 0.77；P = 0.006）。还观察到CG基因型和G等位基因携带者（CG/GG基因型）与IPAH风险降低有关。此外，我们发现携带-572GG或GC基因型的个体的IL-6水平显著低于携带-572CC基因型的个体。未发现-6331T/C多态性与IPAH风险或IL-6水平之间存在关联。这些结果表明，IL-6启动子多态性-572C/G而非-6331T/C与血清IL-6水平及IPAH风险相关。
