by Mark E. Engel, Raphaella Stander, Jonathan Vogel, Adebowale A. Adeyemo, Bongani M. Mayosi
Background
Acute rheumatic fever is considered to be a heritable condition, but the magnitude of the genetic effect is unknown.
The object of this work was to lead a systematic review and meta-analysis of twin studies of harmony of acute rheumatic fever in place to derive quantitative estimates of the sizing of the genetic effect.
Methods
We searched PubMed/MEDLINE, ISI Web of Science, EMBASE, and Google Scholar from their origin 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 calculated by probandwise concordance rate and odds ratio (OR), and aggregate probandwise concordance risk was measured 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.
Results
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 connection between zygosity and harmony was strong (OR 6.39; 95% confidence interval, 3.39 to 12.06; P
Conclusions
Acute rheumatic fever is an autoimmune disorder with a high heritability. The breakthrough of all genetic susceptibility loci through whole genome scanning may offer a clinically useful genetic risk prediction tool for acute rheumatic fever and its sequel, rheumatic heart disease.