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首页> 美国卫生研究院文献>BioMed Research International >The -174G/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis
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The -174G/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis

机译：-174G / C白细胞介素6基因启动子多态性作为类风湿关节炎对甲氨蝶呤和来氟米特治疗反应差异的遗传标记

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Objective. To evaluate the association of -174G/C IL-6 polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped for IL-6 -174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2). Results. Patients with MTX or LEF had significant decrement in DAS-28 (p < 0.001); nevertheless, only 14% and 12.5% achieved DAS-28 < 3.2 at 3 and 6 months. After 6 months with any of these drugs the -174G/G genotype carriers (56%) had higher risk of therapeutic failure compared with GC (RR: 1.19, 95% CI: 1.07–1.56). By analyzing each drug separately, after 6 months with LEF, GG genotype confers higher risk of therapeutic failure than GC (RR = 1.56; 95% CI = 1.05–2.3; p = 0.003), or CC (RR = 1.83; 95% CI = 1.07–3.14; p = 0.001). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03–1.72; p = 0.02). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded that IL-6 -174G/G genotype confers higher risk of failure in therapeutic response to LEF in Mexicans and if confirmed in other populations this can be used as promissory genetic marker to differentiate risk of therapeutic failure to LEF.
机译：目的。评估-174G / C IL-6多态性与对甲氨蝶呤（MTX）或来氟米特（LEF）的治疗反应失败的关联。这项前瞻性观察性队列研究纳入了96名患有中度或重度类风湿关节炎（RA），开始MTX或LEF的墨西哥-Mestizo患者，并通过PCR-RFLP对IL-6 -174G / C多态性进行了基因分型。严格定义治疗反应：仅当患者达到缓解或疾病活动低（DAS-28 <3.2）时。结果。患有MTX或LEF的患者DAS-28明显减少（p <0.001）；但是，在3个月和6个月时，只有14％和12.5％的DAS-28达到<3.2。与GC相比，使用任何一种药物治疗6个月后，-174G / G基因型携带者（56％）具有更高的治疗失败风险（RR：1.19，95％CI：1.07-1.56）。通过分别分析每种药物，LEF治疗6个月后，GG基因型的治疗失败风险比GC（RR = 1.56; 95％CI = 1.05–2.3; p = 0.003）或CC（RR = 1.83; 95％CI）高= 1.07–3.14； p = 0.001）。在主导模型中也观察到了这种风险（RR = 1.33； 95％CI = 1.03–1.72； p = 0.02）。相反，在接受MTX的患者中，没有基因型可以预测治疗失败。我们得出的结论是，IL-6 -174G / G基因型在墨西哥人中对LEF的治疗反应失败的风险更高，如果在其他人群中得到证实，则该基因型可以用作区分LEF治疗失败的风险的基因标记。

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