Consejo Superior de Investigaciones Cientificas (CSIC), Granada, Spain.
Clin Exp Rheumatol. 2009 Nov-Dec;27(6):964-70.
To determine whether the interleukin (IL)6 -174 gene polymorphism may influence the development of subclinical atherosclerosis manifested by the presence of endothelial dysfunction in RA patients.
311 patients (228 [73.3%] women; 243 [78.1%] rheumatoid factor positive) who fulfilled the 1987 ACR classification criteria for RA seen at the Rheumatology outpatient clinic of Hospital Xeral-Calde, Lugo between March 1996 and December 2006 and 226 matched controls were included in this study. Between March and December 2007, a subgroup of 98 patients randomly selected was assessed for the presence of endothelial dysfunction. Patients and controls were genotyped for a single biallelic (G/C) nucleotide polymorphism (rs1800795) in the promoter region at the position -174 of the IL6 gene using a TaqMan 5' allele discrimination assay.
No significant differences in the IL6 -174 allele or genotype frequency between RA patients and controls were found. However, RA patients homozygous for the IL6 -174 GG genotype had more severe endothelial dysfunction (flow-mediated endothelium-dependent vasodilatation-FMD%: 4.2 + or - 6.6) than those carrying the IL6 -174 GC (FMD%: 6.3 + or - 8.1) or IL6 -174 CC (FMD%: 6.0 + or - 3.3) genotypes. In this regard, significant differences were observed when FMD% values in RA patients carrying the IL6 -174 GG genotype were compared with that observed in those carrying the IL6 -174 GC and the IL6 -174 CC genotypes (FMD%: 6.3 + or - 4.6) (p=0.02).
Our results support a role of IL6 -174 gene polymorphism in the development of subclinical atherosclerosis in patients with RA.
确定白细胞介素（IL）6-174 基因多态性是否会影响类风湿关节炎（RA）患者亚临床动脉粥样硬化的发展，其表现为内皮功能障碍。
本研究共纳入 311 例患者（228 例[73.3%]为女性；243 例[78.1%]类风湿因子阳性），这些患者于 1996 年 3 月至 2006 年 12 月在拉戈的 Xeral-Calde 医院的风湿病门诊就诊，并符合 1987 年 ACR 分类标准诊断为 RA，同时还纳入了 226 例匹配对照者。在 2007 年 3 月至 12 月期间，随机选择了一组 98 例患者评估内皮功能障碍。采用 TaqMan5'等位基因鉴别分析方法，对 IL6 基因启动子区域的 -174 位的单个双等位基因（G/C）核苷酸多态性（rs1800795）对患者和对照者进行基因分型。
RA 患者与对照组之间，IL6-174 等位基因或基因型频率无显著差异。然而，IL6-174 GG 基因型纯合的 RA 患者的内皮功能障碍更严重（血流介导的内皮依赖性血管舒张-FMD%：4.2+/-6.6），而携带 IL6-174 GC（FMD%：6.3+/-8.1）或 IL6-174 CC（FMD%：6.0+/-3.3）基因型的患者则较轻。在这方面，当比较携带 IL6-174 GG 基因型的 RA 患者的 FMD%值与携带 IL6-174 GC 和 IL6-174 CC 基因型的患者的 FMD%值（FMD%：6.3+/-4.6）时，观察到了显著差异（p=0.02）。
我们的研究结果支持 IL6-174 基因多态性在 RA 患者亚临床动脉粥样硬化发展中的作用。
