心血管事件与 MTHFR 多态性无关，但与美国类风湿关节炎退伍军人中使用甲氨蝶呤和传统危险因素有关。
Cardiovascular events are not associated with MTHFR polymorphisms, but are associated with methotrexate use and traditional risk factors in US veterans with rheumatoid arthritis.
机构信息
Department of Rheumatology, University of Colorado School of Medicine, Denver, CO, USA.
出版信息
J Rheumatol. 2013 Jun;40(6):809-17. doi: 10.3899/jrheum.121012. Epub 2013 Apr 1.
OBJECTIVE
C677T and A1298C polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with increased cardiovascular (CV) events in non-rheumatoid arthritis (RA) populations. We investigated potential associations of MTHFR polymorphisms and use of methotrexate (MTX) with time-to-CV event in data from the Veterans Affairs Rheumatoid Arthritis (VARA) registry.
METHODS
VARA participants were genotyped for MTHFR polymorphisms. Variables included demographic information, baseline comorbidities, RA duration, autoantibody status, and disease activity. Patients' comorbidities and outcome variables were defined using International Classification of Diseases-9 and Current Procedural Terminology codes. The combined CV event outcome included myocardial infarction (MI), percutaneous coronary intervention, coronary artery bypass graft surgery, and stroke. Cox proportional hazards regression was used to model the time-to-CV event.
RESULTS
Data were available for 1047 subjects. Post-enrollment CV events occurred in 97 patients (9.26%). Although there was a trend toward reduced risk of CV events, MTHFR polymorphisms were not significantly associated with time-to-CV event. Time-to-CV event was associated with prior stroke (HR 2.01, 95% CI 1.03-3.90), prior MI (HR 1.70, 95% CI 1.06-2.71), hyperlipidemia (HR 1.57, 95% CI 1.01-2.43), and increased modified Charlson-Deyo index (HR 1.23, 95% CI 1.13-1.34). MTX use (HR 0.66, 95% CI 0.44-0.99) and increasing education (HR 0.87, 95% CI 0.80-0.95) were associated with a lower risk for CV events.
CONCLUSION
Although MTHFR polymorphisms were previously associated with CV events in non-RA populations, we found only a trend toward decreased association with CV events in RA. Traditional risk factors conferred substantial CV risk, while MTX use and increasing years of education were protective.
目的
亚甲基四氢叶酸还原酶（MTHFR）中的 C677T 和 A1298C 多态性与非类风湿关节炎（RA）人群中的心血管（CV）事件增加有关。我们研究了 MTHFR 多态性与接受甲氨蝶呤（MTX）治疗的患者发生 CV 事件时间之间的潜在关联，这些数据来自退伍军人事务部 RA 登记处（VARA）。
方法
对 VARA 参与者进行 MTHFR 多态性基因分型。变量包括人口统计学信息、基线合并症、RA 持续时间、自身抗体状态和疾病活动度。患者的合并症和结局变量使用国际疾病分类第 9 版和当前程序术语代码定义。复合 CV 事件结局包括心肌梗死（MI）、经皮冠状动脉介入治疗、冠状动脉旁路移植术和中风。使用 Cox 比例风险回归模型来模拟 CV 事件时间。
结果
共纳入 1047 例患者的数据。97 例患者（9.26%）发生了登记后 CV 事件。尽管 CV 事件的风险呈下降趋势，但 MTHFR 多态性与 CV 事件时间无显著相关性。CV 事件时间与既往中风（HR 2.01，95%CI 1.03-3.90）、既往 MI（HR 1.70，95%CI 1.06-2.71）、高脂血症（HR 1.57，95%CI 1.01-2.43）和增加的改良 Charlson-Deyo 指数（HR 1.23，95%CI 1.13-1.34）相关。MTX 治疗（HR 0.66，95%CI 0.44-0.99）和受教育程度增加（HR 0.87，95%CI 0.80-0.95）与 CV 事件风险降低相关。
结论
尽管 MTHFR 多态性先前与非 RA 人群的 CV 事件相关，但我们仅发现 RA 患者 CV 事件的相关性呈下降趋势。传统危险因素导致了大量的 CV 风险，而 MTX 治疗和受教育年限的增加具有保护作用。
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