The familial aggregation of rheumatoid arthritis and its relationship to the HLA-DR4 association.
The familial aggregation of rheumatoid arthritis and its relationship to the HLA-DR4 association.
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DOI：
10.1093/oxfordjournals.aje.a113802
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发表时间：
1984-05
影响因子：
5
通讯作者：
D. D. del Junco-D.;H. Luthra;J. Annegers;J. Worthington;L. Kurland
中科院分区：
文献类型：
--
作者：
D. D. del Junco-D.;H. Luthra;J. Annegers;J. Worthington;L. Kurland
本研究对明尼苏达州罗切斯特类风湿性关节炎的家族聚集性进行了调查，这是由于以前的报告存在相当大的变异性，并且需要根据最近建立的人类淋巴细胞抗原（HLA）-DR 4相关性来解释调查结果。采用历史队列方法，确定78名先证者的1631名生物学亲属中成人发病类风湿性关节炎的发病率，并与罗切斯特人群的发病率进行比较。与一般人群相比，一级亲属的年龄和性别调整率为1.7（95%置信区间1.0-2.9）。这种增加集中在16至40岁年龄组，表明存在某种疾病异质性。然而，先证者的性别、血清学阳性、年龄或父母疾病状态对家族性风险水平没有显著影响。将这些发现与先前的研究相结合，在先前的研究中，病例确定是完整的，得出结论，类风湿性关节炎的家族聚集性很弱。弱家族聚集性和已知的强HLA-DR 4与类风湿性关节炎之间的明显差异通过检查两种不同类型研究中关联性测量之间的数学关系来解决。结果表明，要与弱家族聚集性相一致，任何推定的易感基因必须具有非常低的等位基因频率，和/或必须有大量的散发病例残留。
This investigation of the familial aggregation of rheumatoid arthritis in Rochester, Minnesota, was prompted by the considerable variability in previous reports and the need to interpret findings in light of the recently established human lymphocyte antigen (HLA)-DR4 association. The historical cohort methodology was applied to determine the incidence of adult-onset rheumatoid arthritis in 1631 biologic relatives of 78 probands compared with the Rochester population incidence. The ratio of the age- and sex-adjusted rates in first-degree relatives compared with the general population was 1.7 (95% confidence interval 1.0-2.9). The increase was concentrated in the 16- to 40-year-old age group, suggesting some disease heterogeneity. However, the level of familial risk was not significantly affected by the proband's sex, seropositivity, age, or parental disease status. Integrating these findings with prior research in which case ascertainment was complete led to the conclusion that familial aggregation of rheumatoid arthritis is weak. The apparent discrepancy between weak familial aggregation and the known strong HLA-DR4 association with rheumatoid arthritis was resolved by examining the mathematical relationship between the measures of association in the two different types of studies. Results show that to be consistent with weak familial clustering, any putative susceptibility gene must have very low penetrance, and/or there must be a large residual of sporadic cases.