Smoking and disease severity in rheumatoid arthritis - Association with polymorphism at the glutathione S-transferase M1 locus
Smoking and disease severity in rheumatoid arthritis - Association with polymorphism at the glutathione S-transferase M1 locus
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DOI：
10.1002/art.10174
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发表时间：
2002-03-01
影响因子：
--
通讯作者：
Strange, RC
中科院分区：
文献类型：
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作者：
Mattey, DL;Hutchinson, D;Strange, RC
objective.研究吸烟与女性类风湿关节炎（RA）患者疾病严重程度的关系是否与谷胱甘肽S-转移酶（GST）M1位点多态性有关。采用聚合酶链反应方法对164例确诊的RA患者进行GSTM 1基因分型。每例患者均获得吸烟史。影像学损害通过Larsen评分进行测量，功能结局通过健康评估问卷（HAQ）进行评估。数据采用多元回归分析，并对年龄和病程进行校正。曾经吸烟者的影像学和功能预后比从不吸烟者差。过去和现在的吸烟都与疾病严重程度增加有关。分层的GSTM 1状态显示，在这个位点的多态性影响吸烟和疾病的结果措施之间的关系。缺乏GSTM1基因且曾经吸烟的患者比缺乏该基因且从不吸烟的患者有更高的Larsen和HAQ评分。这些患者的影像学结果比有GSTM 1基因和吸烟的患者更差。这些协会没有受到社会经济地位校正的影响。仅在GSTM1基因敲除的患者中发现与吸烟相关的风湿因子（RF）的产生。我们的数据表明，有吸烟史的女性类风湿关节炎患者的疾病结局明显比从不吸烟的患者差。在携带GSTM1-null多态性的患者中，吸烟与最严重的疾病相关。这种关联可能部分是由于GSTM1多态性和吸烟者RF产生之间的关系。
Objective. To determine whether the relationship between smoking and disease severity in women with rheumatoid arthritis (RA) is associated with polymorphism at the glutathione S-transferase (GST) M1 locus.Methods. Genotyping for GSTM1 was carried out using polymerase chain reaction methodology on 164 women with established RA. Smoking history was obtained on each patient. Radiographic damage was measured by the Larsen score, and functional outcome was assessed by the Health Assessment Questionnaire (HAQ). Data were analyzed by multiple regression analyses, with correction for age and disease duration.Results. Ever having smoked was associated with a worse radiographic and functional outcome than was never having smoked. Both past and current smoking were associated with increased disease severity. Stratification by GSTM1 status revealed that polymorphism at this locus affected the relationship between smoking and disease outcome measures. Patients who lacked the GSTM1 gene and had ever smoked had significantly higher Larsen and HAQ scores than did those who lacked the gene and had never smoked. Radiographic outcome in these patients was worse than that in patients who had the GSTM1 gene and who had smoked. The associations were not affected by correction for socioeconomic status. Rheumatoid factor (RF) production was found to be associated with smoking in only the GSTM1-null patients.Conclusion. Our data suggest that disease outcome in female RA patients with a history of smoking is significantly worse than in those who have never smoked. Smoking was associated with the most severe disease in patients who carried the GSTM1-null polymorphism. This association may be due in part to a relationship between the GSTM1 polymorphism and RF production in smokers.