Gene-environment interaction between HLA-DRB1 shared epitope and heavy cigarette smoking in predicting incident rheumatoid arthritis.
Gene-environment interaction between HLA-DRB1 shared epitope and heavy cigarette smoking in predicting incident rheumatoid arthritis.
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DOI：
10.1136/ard.2008.102962
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发表时间：
2010-01
影响因子：
27.4
通讯作者：
Costenbader KH
中科院分区：
文献类型：
--
作者：
Karlson EW;Chang SC;Cui J;Chibnik LB;Fraser PA;De Vivo I;Costenbader KH
先前的研究报道了吸烟与人类白细胞抗原(HLA)-DRB1共享表位（SE）基因型的存在和类风湿关节炎（RA）风险之间的相互作用。为了解决剂量的影响，在两个前瞻性队列中进行了一项病例对照研究，以确定重度吸烟与HLA-SE之间的相互作用。从护士健康研究中的32 826名妇女和护士健康研究II中的29 611名妇女中获得血液。偶发类风湿性关节炎的诊断通过图表复习进行验证。对照组的年龄、绝经状态和绝经后激素使用情况相匹配。对SE等位基因进行高分辨率HLA-DRB1基因分型。采用条件logistic回归模型对HLA-SE、吸烟、HLA-SE*吸烟相互作用和RA风险进行评估，并对年龄和生殖因素进行调整。测试了加性和乘性相互作用。总共包括了439对匹配的高加索人。RA诊断时的平均年龄为55.2岁；62%的病例血清呈阳性。在血清阳性RA风险中，观察到吸烟与HLA-SE之间存在适度的加性相互作用。强加性相互作用(相互作用归因比例(AP) = 0.50；p<0.001)和显著的乘法交互作用（p = 0.05）之间发现重度吸烟（bbb10包年）和血清阳性RA风险的任何HLA-SE。风险最高的是双副本HLA-SE的重度吸烟者（优势比（OR） 7.47, 95% CI 2.77 ~ 20.11）。当以吸烟的包年数而不是曾经吸烟进行分层时，观察到HLA-SE与吸烟之间存在强烈的基因-环境相互作用。未来的研究应该在检测基因与吸烟的相互作用时评估吸烟的累积暴露。
Previous studies have reported an interaction between ever cigarette smoking and the presence of the human leukocyte antigen (HLA)-DRB1 shared epitope (SE) genotype and rheumatoid arthritis (RA) risk. To address the effect of dosage, a case-control study nested within two prospective cohorts to determine the interaction between heavy smoking and the HLA-SE was conducted. Blood was obtained from 32 826 women in the Nurses’ Health Study and 29 611 women in the Nurses’ Health Study II. Incident RA diagnoses were validated by chart review. Controls were matched for age, menopausal status and postmenopausal hormone use. High-resolution HLA-DRB1 genotyping was performed for SE alleles. HLA-SE, smoking, HLA-SE* smoking interactions and RA risk, were assessed using conditional logistic regression models, adjusted for age and reproductive factors. Additive and multiplicative interactions were tested. In all, 439 Caucasian matched pairs were included. Mean age at RA diagnosis was 55.2 years; 62% of cases were seropositive. A modest additive interaction was observed between ever smoking and HLA-SE in seropositive RA risk. A strong additive interaction (attributable proportion due to interaction (AP) = 0.50; p<0.001) and significant multiplicative interaction (p = 0.05) were found between heavy smoking (>10 pack-years) and any HLA-SE in seropositive RA risk. The highest risk was in heavy smokers with double copy HLA-SE (odds ratio (OR) 7.47, 95% CI 2.77 to 20.11). A strong gene–environment interaction was observed between HLA-SE and smoking when stratifying by pack-years of smoking rather than by ever smoking. Future studies should assess cumulative exposure to cigarette smoke when testing for gene–smoking interactions.
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影响因子：
13.6
作者：
Andersson, T;Alfredsson, L;Ahlbom, A
通讯作者：
Ahlbom, A
影响因子：
4.9
作者：
Costenbader KH;Chang SC;De Vivo I;Plenge R;Karlson EW
通讯作者：
Karlson EW
影响因子：
27.4
作者：
HAZES, JMW;DIJKMANS, BAC;CATS, A
通讯作者：
CATS, A
影响因子：
27.4
作者：
Criswell, L. A.;Saag, K. G.;Seldin, M. F.
通讯作者：
Seldin, M. F.
影响因子：
27.4
作者：
Makrygiannakis, D.;Hermansson, M.;Catrina, A. I.
通讯作者：
Catrina, A. I.