Influence of male sex on disease phenotype in familial rheumatoid arthritis
Influence of male sex on disease phenotype in familial rheumatoid arthritis
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DOI：
10.1002/art.22120
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发表时间：
2006-10-01
影响因子：
--
通讯作者：
Criswell, Lindsey A.
中科院分区：
文献类型：
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作者：
Jawaheer, Damini;Lum, Raymond F.;Criswell, Lindsey A.
Objective.研究家族性类风湿关节炎（RA）患者在临床、人口统计学和遗传学特征方面的性别差异。我们研究了从北美风湿性关节炎协会招募的467个高加索多酶RA家族的1,004名受影响成员。从所有患者中收集有关人口统计学和临床特征的标准化信息。受影响的个人也进行了X光摄影的手，并在HLA区域的标记基因分型。性别差异采用列联表分析（分类变量）和学生t检验（连续变量），并通过多变量logistic和线性回归分析进行评估。与女性患者相比，男性患者的RA发病明显较晚，更可能是RF血清阳性，并且抗环瓜氨酸肽（抗CCP）抗体滴度明显较高，即使在多变量分析中调整协变量后也是如此。男性患者也更有可能有吸烟史并且HLA-DRB 1共享表位（SE）呈阳性。有趣的是，与没有受影响的男性兄弟姐妹的女性患者相比，有受影响的男性兄弟姐妹的女性患者的抗CCP抗体滴度显着更高，更可能是SE阳性。多因素分析表明，SE的存在并不能完全解释在这些家庭中观察到的抗CCP抗体滴度增加。性别对RA的疾病表型有重要影响，包括发病年龄和自身抗体的产生。此外，受影响的男性成员的家庭的特点是较高滴度的自身抗体，特别是抗CCP抗体。我们的结果表明，这些发现并不能完全用烟草烟雾暴露、HLA-DRIB 1 SE或其他HLA区域遗传变异的存在差异来解释。因此，其他遗传或非遗传因素也有助于RA表型的性别差异。
Objective. To examine sex differences in clinical, demographic, and genetic characteristics among a large cohort of patients with familial rheumatoid arthritis (RA).Methods. We studied 1,004 affected members of 467 Caucasian multicase RA families recruited from the North American Rheumatoid Arthritis Consortium. Standardized information about demographic and clinical characteristics was collected from all patients. Affected individuals also underwent radiography of the hands and were genotyped for markers in the HLA region. Sex differences were assessed using contingency table analysis (for categorical variables) and Student's t-tests for (continuous variables), and by multivariate logistic and linear regression analysis.Results. Male patients had a significantly later onset of RA, were more likely to be seropositive for RF, and had significantly higher titers of anti-cyclic citrul-linated peptide (anti-CCP) antibodies compared with female patients, even after adjustment for covariates in multivariate analyses. Male patients were also significantly more likely to have a history of smoking and to be HLA-DRB1 shared epitope (SE) positive. Interestingly, female patients with an affected male sibling had significantly higher titers of anti-CCP antibodies and were more likely to be SE positive compared with female patients without affected male siblings. Multivariate analyses indicated that the presence of the SE did not fully explain the increased anti-CCP antibody titers observed in these families.Conclusion. Sex has an important influence on the disease phenotype in RA, including the age at disease onset and autoantibody production. Furthermore, families with affected male members are characterized by higher titers of autoantibodies, particularly anti-CCP antibodies. Our results indicate that these findings are not fully explained by differences in exposure to tobacco smoke, presence of the HLA-DRIB1 SE, or other HLA region genetic variation. Thus, other genetic or nongenetic factors also contribute to sex differences in the RA phenotype.