Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.
PLoS One. 2011;6(9):e25326. doi: 10.1371/journal.pone.0025326. Epub 2011 Sep 30.
Acute rheumatic fever is considered to be a heritable condition, but the magnitude of the genetic effect is unknown. The objective of this study was to conduct a systematic review and meta-analysis of twin studies of concordance of acute rheumatic fever in order to derive quantitative estimates of the size of the genetic effect.
We searched PubMed/MEDLINE, ISI Web of Science, EMBASE, and Google Scholar from their inception to 31 January 2011, and bibliographies of retrieved articles, for twin studies of the concordance for acute rheumatic fever or rheumatic heart disease in monozygotic versus dizygotic twins that used accepted diagnostic criteria for acute rheumatic fever and zygosity without age, gender or language restrictions. Twin similarity was measured by probandwise concordance rate and odds ratio (OR), and aggregate probandwise concordance risk was calculated by combining raw data from each study. ORs from separate studies were combined by random-effects meta-analysis to evaluate association between zygosity status and concordance. Heritability was estimated by fitting a variance components model to the data.
435 twin pairs from six independent studies met the inclusion criteria. The pooled probandwise concordance risk for acute rheumatic fever was 44% in monozygotic twins and 12% in dizygotic twins, and the association between zygosity and concordance was strong (OR 6.39; 95% confidence interval, 3.39 to 12.06; P<0.001), with no significant study heterogeneity (P = 0.768). The estimated heritability across all the studies was 60%.
Acute rheumatic fever is an autoimmune disorder with a high heritability. The discovery of all genetic susceptibility loci through whole genome scanning may provide a clinically useful genetic risk prediction tool for acute rheumatic fever and its sequel, rheumatic heart disease.
急性风湿热被认为是一种遗传性疾病，但遗传效应的程度尚不清楚。本研究的目的是对急性风湿热同卵双生子和异卵双生子一致性的双胞胎研究进行系统评价和荟萃分析，以便得出遗传效应大小的定量估计。
我们检索了 PubMed/MEDLINE、ISI Web of Science、EMBASE 和 Google Scholar，从建库到 2011 年 1 月 31 日，以及检索到的文章的参考文献，以寻找符合以下条件的双胞胎研究：使用公认的急性风湿热诊断标准，对同卵双生子和异卵双生子的急性风湿热或风湿性心脏病的一致性进行研究，并且不限制年龄、性别或语言。通过对先证者一致性率和比值比（OR）来衡量双胞胎的相似性，并通过合并每项研究的原始数据来计算聚合的先证者一致性风险。通过随机效应荟萃分析合并来自不同研究的 OR，以评估同卵双生子和异卵双生子之间的一致性与关系。通过拟合方差分量模型对数据进行遗传力估计。
六项独立研究的 435 对双胞胎符合纳入标准。急性风湿热的同卵双生子和异卵双生子的聚集性先证者一致性风险分别为 44%和 12%，同卵双生子和异卵双生子之间的一致性与关系很强（OR 6.39；95%置信区间，3.39 至 12.06；P<0.001），且无显著的研究异质性（P=0.768）。所有研究的遗传力估计值为 60%。
急性风湿热是一种自身免疫性疾病，具有高度遗传性。通过全基因组扫描发现所有的遗传易感性基因座，可能为急性风湿热及其后遗症风湿性心脏病提供一种有临床应用价值的遗传风险预测工具。
