Abstract
BackgroundAcute 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.MethodsWe 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.Results435 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%.ConclusionsAcute 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.
Highlights
Acute rheumatic fever is a multifactorial disorder that is caused by an interaction between a rheumatogenic strain of group A streptococcus and a susceptible host who lives in poor social conditions
[1] While much is known about the social factors and the microbial agent that predispose to acute rheumatic fever, little progress has been made in elucidating genetic susceptibility factors that are reproducible in different populations. [1]
[1] Higher concordance rates between monozygotic twins compared with dizygotic twins indicate a greater role for genetic factors in the development of a disease given that monozygotic twins are genetically identical, versus dizygotic twins who, on average, share 50% of their genes, concordance of a similar magnitude in both monozygotic and dizygotic twin pairs suggests the involvement of factors not pertaining to genes
Summary
Acute rheumatic fever is a multifactorial disorder that is caused by an interaction between a rheumatogenic strain of group A streptococcus and a susceptible host who lives in poor social conditions. The role of a host susceptibility factor that may be common to all human beings is supported by the observation that the lifetime cumulative incidence of acute rheumatic fever in populations who are exposed to untreated group A streptococcal pharyngitis is 3–6% regardless of geography or ethnicity. Several twin and family aggregation studies have suggested a genetic effect, but they have not provided a quantitative estimate of the magnitude of the genetic contribution in acute rheumatic fever. We have conducted a systematic review and meta-analysis of the concordance rate and heritability of acute rheumatic fever in monozygotic and dizygotic twin pairs as reported in observational studies. 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
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