类风湿关节炎的遗传与家族风险

作者:发布时间:2013/12/10 9:54:44

类风湿关节炎的遗传与家族风险

李常虹

摘要(瑞典)目的:在3个大的具有代表性的人群样本中评估类风湿关节炎(RA)家族聚集情况,同时研究这一家族聚集性是否受到类风湿因子(RF)/抗瓜氨酸蛋白抗体(ACPA)、血缘关系类型、性别及RA发病年龄的影响。

方法:本研究是在整个瑞典人群中进行的注册形式的巢式病例对照研究。所有RA患者的资料来源于瑞典全国患者登记中心(n=88639)、瑞典风湿病质控登记中心(n=11519)以及RA流行病学调查研究(n=2871)。RA患者一级、二级亲属的相关资料来源于瑞典多代登记中心。研究应用条件逻辑回归方法评估亲属患RA的家族风险。

结果:三大数据来源均得出了一致性的结论,RA患者一级亲属患病的家族风险比为3,二级亲属患病的家族风险比为2。这一家族风险在RA患者的兄弟姐妹、父母及子女中没有差异。同时家族聚集性也不受性别的影响,但对于RF/ACPA阳性和年轻时起病的RA患者家族聚集性要高一些。在ACPA阳性的RA患者中家族风险遗传可能性为50%,在ACPA阴性的患者中家族风险遗传可能性为20%。

结论:这些危险因素的形式提示家族因素对于RA影响在男性和女性之间是没有差异,并且这些影响因素对于晚发型RA的影响要小于年轻时起病的RA。家族因素对于血清阳性的RA患者影响明显,但血清阳性的RA患者和血清阴性的RA患者间往往有家族重叠现象。虽然家族风险一般认为是完全遗传来的,但实际观察显示RA的遗传可能性要低于先前的报道,尤其是ACPA阴性的RA患者。

附原文:Objective. To estimate familial aggregation of rheumatoid arthritis (RA) in 3 large population-representative samples and to test if familial aggregation is affected by rheumatoid factor (RF)/anti–citrullinated protein antibody (ACPA) status, type of relative, sex, and age at onset of RA.Methods. A register-based nested case–control study was performed in the Swedish total population.Data on patients with RA were ascertained through the nationwide Swedish Patient Register (n _ 88,639), the clinical Swedish Rheumatology Quality Register (n-11,519), and the Epidemiological Investigation of Rheumatoid Arthritis case–control study (n-2,871). Data on first- and second-degree relatives were obtained through the Swedish Multigeneration Register. Familial risks were calculated using conditional logistic regression. Results. Consistent across data sources, the familial odds ratio for RA was ~3 in first-degree relatives of RA patients and 2 in second-degree relatives. Familial risks were similar among siblings, parents, and offspring. Familial aggregation was not modified by sex, but was higher in RA patients with early-onset disease and in RF/ACPA-positive RA patients. The observed familial risks were consistent with a heritability of ~50% for ACPA-positive RA and ~20% for ACPA negative RA. Conclusion. The pattern of risks suggests that familial factors influence RA in men and women equally and that these factors are of less importance for lateonset RA. Familial factors are more important for seropositive RA, but there is significant familial overlap between seropositive RA and seronegative RA. Even if the familial risk is assumed to be completely due to genetics, the observed risks suggest that heritability of RA is lower than previously reported, in particular for ACPA-negative RA.

引自:Thomas Frisell, Marie Holmqvist, Henrik K berg, Lars Klareskog, Lars Alfredsson, and Johan Askling, Familial Risks and Heritability of Rheumatoid Arthritis. ARTHRITIS & RHEUMATISM Vol. 65, No. 11, November 2013, pp 2773–2782.