Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease

Jane C. Burns, Chisato Shimizu, Enrique Gonzalez, Hemant Kulkarni, Sukeshi Patel, Hiroko Shike, Robert S. Sundel, Jane W. Newburger, Sunil K. Ahuja

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Kawasaki disease (KD) is an enigmatic, self-limited vasculitis of childhood that is complicated by development of coronary-artery aneurysms. The high incidence of KD in Asian versus European populations prompted a search for genetic polymorphisms that are differentially distributed among these populations and that influence KD susceptibility. Here, we demonstrate a striking, inverse relationship between the worldwide distribution of CCR5-Δ32 allele and the incidence of KD. In 164 KD patient-parent trios, 4 CCR5 haplotypes including the CCR5-Δ32 allele were differentially transmitted from heterozygous parents to affected children. However, the magnitude of the reduced risk of KD associated with the CCR5-Δ32 allele and certain CCR5 haplotypes was significantly greater in individuals who also possessed a high copy number of the gene encoding CCL3L1, the most potent CCR5 ligand. These findings, derived from the largest genetic study of any systemic vasculitis, suggest a central role of CCR5-CCL3L1 gene-gene interactions in KD susceptibility and the importance of gene modifiers in infectious diseases.

Original languageEnglish (US)
Pages (from-to)344-349
Number of pages6
JournalJournal of Infectious Diseases
Volume192
Issue number2
DOIs
StatePublished - Jul 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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