Gene-environment interaction between the DRB1 shared epitope and smoking in the risk of anti-citrullinated protein antibody-positive rheumatoid arthritis: all alleles are important.
Gene-environment interaction between the DRB1 shared epitope and smoking in the risk of anti-citrullinated protein antibody-positive rheumatoid arthritis: all alleles are important.
复制标题
DOI：
10.1002/art.24572
复制
发表时间：
2009-06
影响因子：
--
通讯作者：
Padyukov, Leonid
中科院分区：
文献类型：
--
作者：
Lundstrom, Erneli;Kallberg, Henrik;Alfredsson, Lars;Klareskog, Lars;Padyukov, Leonid
HLA-DRB 1共享表位（SE）等位基因与吸烟之间存在相互作用，从而导致风湿性关节炎（RA）的发生。我们的目的是进一步研究不同的SE等位基因和吸烟之间的相互作用，在有和没有瓜氨酸化蛋白抗原（ACPA）抗体的情况下发生RA的风险。使用来自EIRA研究的1319名患者和943名对照的吸烟习惯和HLA-DRB 1基因型数据，其中972名患者和488名对照为SE阳性。随后，对759例病例和328例对照进行了 *04组内特定等位基因的亚型分析。采用Logistic回归分析计算OR值及95%可信区间（95%CI）。通过计算归因于相互作用的比例（AP）和95% CI评价相互作用。将所有DRB 1 *04 SE等位基因作为一个组，观察到吸烟和SE等位基因在ACPA阳性RA的发展中存在强烈的相互作用（RR：8.7 95% CI：5.7-13.1）或 *0401和 *0404等位基因（RR：8.9 95% CI：5.8-13.5），*01和 *10等位基因为特异性独立组（RR：4.9 95% CI：3.0-7.8），不同组AP的相互作用强度相似：分别为0.4（0.2-0.6）、0.5（0.3-0.7）和0.6（0.4-0.8）。在ACPA阳性RA的发生中，不同的DRB 1 SE等位基因和吸烟之间存在统计学显著的相互作用。相互作用存在于 *04组以及 *01/*10组中，这表明，无论精细特异性如何，所有SE等位基因都与吸烟强烈相互作用，增加了ACPA阳性RA的风险。
An interaction effect for developing Rheumatoid Arthritis (RA) was previously observed between HLA-DRB1 shared epitope (SE) alleles and smoking. We aimed to further investigate this interaction between distinct SE alleles and smoking regarding risk of developing RA with and without antibodies toward citrullinated protein antigens (ACPA). Data regarding smoking habits and HLA-DRB1 genotypes from 1319 patients and 943 controls from the EIRA study were utilized where 972 patients and 488 controls were SE positive. Subsequently, 759 cases and 328 controls were subtyped for specific alleles within the *04 group. The odds ratios (OR) with 95% confidence interval (95% CI) were calculated by means of logistic regression. Interaction was evaluated by calculating attributable proportion due to interaction (AP) with 95% CI. A strong interaction between smoking and SE alleles in development of ACPA-positive RA was observed regarding both all DRB1*04 SE alleles taken as a group (RR: 8.7 95% CI: 5.7-13.1) or the *0401 and*0404 alleles (RR: 8.9 95% CI: 5.8-13.5) and the *01 and *10 alleles as specific, separate groups (RR: 4.9 95% CI: 3.0-7.8) with similar strength of interaction for the different groups AP: 0.4 (0.2-0.6), 0.5 (0.3-0.7) and 0.6 (0.4-0.8), respectively. A statistically significant interaction is evident between distinct DRB1 SE alleles and smoking in development of ACPA-positive RA. Interaction is present in the *04 group as well as in the *01/*10 group, demonstrating that regardless of fine specificity all SE alleles strongly interact with smoking in providing an increased risk for ACPA-positive RA.
登录
查看更多内容
影响因子：
--
作者：
Pratesi, F;Tommasi, C;Migliorini, P
通讯作者：
Migliorini, P
影响因子：
158.5
作者：
Plenge, Robert M.;Seielstad, Mark;Gregersen, Peter K.
通讯作者：
Gregersen, Peter K.
影响因子：
13.6
作者：
Andersson, T;Alfredsson, L;Ahlbom, A
通讯作者：
Ahlbom, A
影响因子：
--
作者：
Pedersen, Merete;Jacobsen, Soren;Frisch, Morten
通讯作者：
Frisch, Morten
影响因子：
9.8
作者：
Plenge, RM;Padyukov, L;Rioux, JD
通讯作者：
Rioux, JD