Carroll Lisa, Frazer Ian H, Turner Malcolm, Marwick Thomas H, Thomas Ranjeny
Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Brisbane, Queensland 4102, Australia.
Arthritis Res Ther. 2007;9(2):R39. doi: 10.1186/ar2175.
Patients with rheumatoid arthritis (RA) are at risk of excess mortality, predominantly owing to cardiovascular (CV) events. The receptor for advanced glycation end products (RAGE) has been implicated in the perpetuation of the chronic inflammatory response in vascular disease. A Gly82-->Ser polymorphism in the RAGE gene, which is associated with enhanced RAGE signaling, is present more frequently in patients with RA than the general population. To investigate whether RAGE Gly82-->Ser polymorphism is associated with CV events in RA, we examined CV events, CV risk factors, features of RA and RAGE Gly82-->Ser polymorphism in 232 patients with RA attending a tertiary referral hospital. CV events, the duration and severity of RA, and risk factors for CV disease were determined using patient questionnaires, chart review, laboratory analysis and radiographs. DNA was typed for HLA-DRB1 genes and RAGE Gly82-->Ser polymorphism. The RAGE Ser82 allele, which is in linkage disequilibrium with the RA susceptibility allele HLA-DRB1*0401, was carried by 20% of patients. More than 20% of the cohort had suffered a vascular event; a shorter duration of RA, but not the RAGE genotype, was significantly associated with CV events. However, a history of statin use was protective. Thus, the RAGE Ser82 allele, associated with enhanced RAGE signaling, does not predispose to CV events in RA. However, treatment of hyperlipidemia with statins reduces the probability of a CV event.
类风湿关节炎（RA）患者存在额外死亡风险，主要归因于心血管（CV）事件。晚期糖基化终末产物受体（RAGE）与血管疾病慢性炎症反应的持续存在有关。RAGE基因中的一个Gly82→Ser多态性与增强的RAGE信号传导相关，在RA患者中比普通人群更频繁出现。为了研究RAGE Gly82→Ser多态性是否与RA患者的CV事件相关，我们在一家三级转诊医院对232例RA患者的CV事件、CV危险因素、RA特征和RAGE Gly82→Ser多态性进行了检查。通过患者问卷、病历审查、实验室分析和X光片确定CV事件、RA的病程和严重程度以及CV疾病的危险因素。对HLA - DRB1基因和RAGE Gly82→Ser多态性进行DNA分型。RAGE Ser82等位基因与RA易感性等位基因HLA - DRB1*0401处于连锁不平衡状态，20%的患者携带该等位基因。超过20%的队列发生过血管事件；RA病程较短与CV事件显著相关，但与RAGE基因型无关。然而，使用他汀类药物的病史具有保护作用。因此，与增强的RAGE信号传导相关的RAGE Ser82等位基因不会使RA患者易患CV事件。然而，用他汀类药物治疗高脂血症可降低CV事件的发生概率。
