-174G/C 白细胞介素 6 基因启动子多态性作为预测抗肿瘤坏死因子治疗效果的遗传标志物的确认。
Confirmation of -174G/C interleukin-6 gene promoter polymorphism as a genetic marker predicting antitumor necrosis factor treatment outcome.
机构信息
aInstituto de Parasitología y Biomedicina López-Neyra, CSIC bDepartment of Clinical Pharmacy, UGC Farmacia Granada cDepartment of Rheumatology, Instituto de Investigación Biosanitaria de Granada, San Cecilio University Hospital, Granada Departments of dImmunology eRheumatology, IdiPAZ, RIER, La Paz University Hospital, Madrid fDepartment of Rheumatology, Virgen de la Arrixaca University Hospital, Murcia gDepartment of Rheumatology, Virgen de la Victoria University Hospital, Málaga hDepartment of Rheumatology, Doctor Peset Hospital, Valencia, Spain.
出版信息
Pharmacogenet Genomics. 2014 Jan;24(1):1-5. doi: 10.1097/FPC.0000000000000013.
BACKGROUND
The IL-6 -174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA.
MATERIALS AND METHODS
Our study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 -174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion.
RESULTS
The -174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29-6.70], 18 (P=4.54E-03, OR=5.17, 95% CI 1.80-14.85), and 24 months (P=4.54E-03, OR=14.86, 95% CI 2.91-75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E-02, OR=1.80, 95% CI 1.13-2.87, at 12 months).
CONCLUSION
Our results support the role of the -174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.
背景
白细胞介素 6（IL-6）-174G/C 基因变异最近与类风湿关节炎（RA）患者接受依那西普治疗的临床反应相关。考虑到之前的结果，我们的研究目的是验证该多态性作为 RA 患者抗肿瘤坏死因子（anti-TNF）治疗结果预测因子的作用。
材料和方法
我们的研究人群由 199 名接受抗 TNF 治疗的西班牙 RA 患者组成。采用 TaqMan 等位基因鉴别技术对 IL-6-174G/C（rs1800795）基因变异进行基因分型。根据欧洲抗风湿病联盟（EULAR）标准，患者被分类为应答者（良好和中度应答）和无应答者，在首次输注后 6、12、18 和 24 个月。
结果
-174*G 等位基因与 12 个月时的良好或中度 EULAR 反应显著相关[P=0.015，优势比（OR）=2.93，95%置信区间（CI）1.29-6.70]、18 个月（P=4.54E-03，OR=5.17，95% CI 1.80-14.85）和 24 个月（P=4.54E-03，OR=14.86，95% CI 2.91-75.91）。对这些数据进行的荟萃分析与之前的一项研究结果相结合，证实了这种相关性（P=1.89E-02，OR=1.80，95% CI 1.13-2.87，在 12 个月时）。
结论
我们的结果支持-174G/C IL-6 多态性作为抗 TNF 治疗反应性的遗传标志物的作用。
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