Birru Talabi Mehret, Mackey Rachel H, Kuller Lewis H, Dorman Janice S, Deane Kevin D, Robinson William H, Walitt Brian T, Chang Yuefang, Holers V Michael, Liu Simin, Moreland Larry W
Am J Epidemiol. 2017 Jul 15;186(2):245-254. doi: 10.1093/aje/kwx087.
Specific alleles of the human leukocyte antigen (HLA)-DRB1 gene (HLA-DRB1) encode a "shared epitope" (SE) associated with rheumatoid arthritis (RA), especially more severe cyclic-citrullinated peptide antibody-positive (anti-CCP+) RA. We evaluated associations of number of SE alleles (0, 1, or 2) with total and cardiovascular disease (CVD) mortality and incident coronary heart disease (CHD), CVD, and cancer over a mean 8.9 (standard deviation, 3.5) years of follow-up, stratifying by baseline anti-CCP status (positive (+) vs. negative (-)). A longitudinal study, the Women's Health Initiative RA Study (1993-2010), sampled postmenopausal women who reported RA at baseline (1993-1998) or follow-up in the Women's Health Initiative, classified as anti-CCP+ RA (n = 556) or anti-CCP- non-RA (n = 1,070). Among anti-CCP+ RA women, SE alleles were not related to age-adjusted risks of CHD, CVD, or cancer or to total or CVD mortality. Among anti-CCP- non-RA women, age-adjusted hazard ratios for 1 and 2 SE alleles versus 0 SE alleles were 0.41 (95% confidence interval (CI): 0.34, 0.50) and 0.44 (95% CI: 0.27, 0.72), respectively, for CVD; 0.43 (95% CI: 0.37, 0.53) and 0.30 (95% CI: 0.16, 0.64), respectively, for CHD; and 0.62 (95% CI: 0.53, 0.73) and 0.52 (95% CI: 0.33, 0.83), respectively, for cancer. Associations persisted after adjustment for CVD risk factors, joint pain, rheumatoid factor positivity, and inflammatory markers (white blood cell count or cytokine level). In future studies, investigators should evaluate SE associations among anti-CCP- adults without RA and potential mechanisms.
人类白细胞抗原（HLA）-DRB1基因（HLA-DRB1）的特定等位基因编码一种与类风湿关节炎（RA）相关的“共同表位”（SE），尤其是与更严重的环瓜氨酸肽抗体阳性（抗CCP+）RA相关。我们评估了SE等位基因数量（0、1或2个）与在平均8.9年（标准差3.5年）的随访期间的全因死亡率和心血管疾病（CVD）死亡率以及冠心病（CHD）、CVD和癌症发病率之间的关联，并按基线抗CCP状态（阳性（+）与阴性（-））进行分层。一项纵向研究，即女性健康倡议RA研究（1993 - 2010年），对在基线（1993 - 1998年）或女性健康倡议随访中报告患有RA的绝经后女性进行抽样，分为抗CCP+ RA（n = 556）或抗CCP-非RA（n = 1070）。在抗CCP+ RA女性中，SE等位基因与经年龄调整的CHD、CVD或癌症风险以及全因或CVD死亡率无关。在抗CCP-非RA女性中，与0个SE等位基因相比，1个和2个SE等位基因的经年龄调整的风险比分别为：CVD为0.41（95%置信区间（CI）：0.34，0.50）和0.44（95%CI：0.27，0.72）；CHD为0.43（95%CI：0.37，0.53）和0.30（95%CI：0.16，0.64）；癌症为0.62（95%CI：0.53，0.73）和0.52（95%CI：0.33，0.83）。在对CVD危险因素、关节疼痛、类风湿因子阳性和炎症标志物（白细胞计数或细胞因子水平）进行调整后，这些关联仍然存在。在未来的研究中，研究人员应评估无RA的抗CCP-成年人中SE的关联以及潜在机制。
