Smoking interacts with genetic risk factors in the development of rheumatoid arthritis among older Caucasian women
Smoking interacts with genetic risk factors in the development of rheumatoid arthritis among older Caucasian women
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DOI：
10.1136/ard.2005.049676
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发表时间：
2006-09-01
影响因子：
27.4
通讯作者：
Seldin, M. F.
中科院分区：
文献类型：
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作者：
Criswell, L. A.;Saag, K. G.;Seldin, M. F.
目的：确定吸烟对类风湿性关节炎(RA)风险的影响是否受人类白细胞抗原DRB1和谷胱甘肽S转移酶M1基因多态性的影响。方法：受试者来自爱荷华州妇女健康研究中嵌套的病例对照研究，这是一项基于人群的绝经后妇女前瞻性队列研究。确定了115例类风湿性关节炎事件，并回顾了病历以确认类风湿性关节炎的诊断。对照组(n=466)与类风湿性关节炎(RA)患者年龄和种族背景相匹配。根据编码RA“共享表位”(SE)序列的等位基因的存在，对受试者进行了HLA-DRB1分型。GSTM1基因分型采用多重聚合酶链式反应方法。结果：吸烟(OR=6.0p=0.004)、SE阳性(OR=4.6p=0.0006)和GSTM1零基因(OR=3.4p=0.007)与RA的危险性呈正相关，且存在显著的基因-环境交互作用(SE交互作用吸烟p=0.034；GSTM1交互作用吸烟p=0.047)。分层分析表明，在缺乏疾病遗传危险因素(即SE阴性或GSTM1存在)的受试者中，暴露于烟草烟雾主要增加了RA的风险。结论：尽管这些发现需要在其他组中得到证实，但该结果支持了在RA等复杂疾病的研究中同时考虑遗传和环境因素及其相互作用的重要性。
Objective: To determine whether the impact of tobacco exposure on rheumatoid arthritis (RA) risk is influenced by polymorphisms at the HLA-DRB1 and glutathione S-transferase M1 (GSTM1) loci.Methods: Subjects were participants from a case-control study nested within the Iowa Women's Health Study, a population based, prospective cohort study of postmenopausal women. Incident RA cases (n = 115) were identified and medical records reviewed to confirm RA diagnosis. Controls without RA (n = 466) were matched with RA cases by age and ethnic background. HLA-DRB1 typing classified subjects according to the presence of alleles encoding the RA "shared epitope'' (SE) sequence. GSTM1 was genotyped using a multiplex polymerase chain reaction assay. Conditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals.Results: Strong positive associations of smoking (OR = 6.0, p = 0.004), SE positivity (OR = 4.6, p = 0.0006), and GSTM1 null genotype (OR = 3.4, p = 0.007) with risk of RA, and significant gene-environment interactions (smoking by SE interaction p = 0.034; smoking by GSTM1 interaction p = 0.047) were observed. Stratified analyses indicated that exposure to tobacco smoke primarily increased the risk of RA among subjects who lacked genetic risk factors for the disease ( that is, SE negative or GSTM1 present).Conclusions: Although these findings require confirmation in other groups, the results support the importance of considering both genetic and environmental factors, and also their interaction, in studies of complex diseases like RA.