Comparison of the influence of the interleukin-1 receptor antagonist gene on the susceptibility and disease pattern of New Zealand and Brazilian cohorts with rheumatic fever

Abstract

Rheumatic fever (RF) is a major medical problem in the developing world and so-called "hotspots", where the incidence is still 20-300 per 100,000 populations, causing about 500,000 deaths per year, not much different era pre-antibiotic era. In previous work we describe the influence of the Interleukin-1 Receptor Antagonist gene (IL1RN) polymorphism in the severity of carditis in a cohort of Brazilians with FR. From 1996 to 2005, the incidence of RF declined significantly in New Zealanders of European descent, while increased in communities of people of Polynesian descendent, which remains around 100 per 100,000 inhabitants. Since these populations are exposed to similar environmental conditions, susceptibility to RF seems to be genetically determined. The purpose of this study is to answer the following questions: (1) the above mentioned findings in the Brazilian population can be replicated in populations of NZ? (2) The IL1RN polymorphism is associated with susceptibility of the Pacific peoples to FR? If the answer is yes, we can postulate that (A) the Brazilian findings are true (B) they are possibly universal, and (C) these genes may influence the phenotype of FR irrespective of environmental variations. The protein encoded by this gene is commercially available and approved for use in children with other inflammatory diseases. These findings could help better understand FR and guide future treatments and preventive approaches. (AU)