Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis - A nationwide case-control study in Denmark
Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis - A nationwide case-control study in Denmark
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DOI：
10.1002/art.22597
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发表时间：
2007-05-01
影响因子：
--
通讯作者：
Frisch, Morten
中科院分区：
文献类型：
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作者：
Pedersen, Merete;Jacobsen, Soren;Frisch, Morten
目标。研究共享表位（SE）易感基因在类风湿关节炎（RA）亚型发病中的作用，该亚型由抗环瓜氨酸肽（ccp）血清抗体的存在或不存在定义。为了解决这些问题，2002-2004年期间在丹麦进行了一项全国性的病例对照研究，包括RA事件病例或最近诊断为RA的患者（309例抗CCP IgG抗体血清阳性和136例血清阴性）和533名性别和年龄匹配的人群对照。通过逻辑回归分析评估相关性，其中优势比（ORs）作为相对风险的衡量标准。与没有SE易感基因的个体相比，SE纯合子患抗ccp阳性RA的风险增加（OR 17.8, 95%可信区间[95% CI] 10.8-29.4），而抗ccp阴性RA的风险没有增加（OR 1.07, 95% CI 0.53-2.18）。观察到强烈的基因-环境联合效应，重度吸烟者（OR 52.6, 95% CI 18.0-154）、重度咖啡饮用者（OR 53.3, 95% CI 15.5-183）或口服避孕药使用者（OR 44.6, 95% CI 15.2-131）的SE纯合子与未暴露于这些环境危险因素的SE非携带者相比，抗ccp阳性RA的风险显著增加。SE易感基因纯合子的人，特别是暴露于环境危险因素的人，患抗ccp阳性RA的风险明显选择性增加。抗ccp阳性RA和抗ccp阴性RA之间的区别似乎是有必要的，因为这些RA亚型最有可能代表病因不同的疾病实体。
Objective. To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs).Methods. To address these issues, a nationwide case-control study was conducted in Denmark during 2002-2004, comprising incident cases of RA or patients with recently diagnosed RA (309 seropositive and 136 seronegative for IgG antibodies against CCP) and 533 sex- and age-matched population controls. Associations were evaluated by logistic regression analyses, in which odds ratios (ORs) served as measures of relative risk.Results. Compared with individuals without SE susceptibility genes, SE homozygotes had an elevated risk of anti-CCP-positive RA (OR 17.8, 95% confidence interval [95% CI] 10.8-29.4) but not anti-CCP-negative RA (OR 1.07, 95% CI 0.53-2.18). Strong combined gene-environment effects were observed, with markedly increased risks of anti-CCP-positive RA in SE homozygotes who were heavy smokers (OR 52.6, 95% CI 18.0-154), heavy coffee drinkers (OR 53.3, 95% CI 15.5-183), or oral contraceptive users (OR 44.6, 95% CI 15.2-131) compared with SE noncarriers who were not exposed to these environmental risk factors.Conclusion. Persons who are homozygous for SE susceptibility genes, notably those who are also exposed to environmental risk factors, have a markedly and selectively increased risk of anti-CCP-positive RA. A distinction between anti-CCP-positive RA and anti-CCP-negative RA seems warranted, because these RA subtypes most likely represent etiologically distinct disease entities.