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High-density genotyping of immune loci in Kawasaki disease and IVIG treatment response in European-American case–parent trio study

Genes & Immunity volume 15, pages 534–542 (2014)Cite this article

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Abstract

Kawasaki disease (KD) is a diffuse and acute small-vessel vasculitis observed in children, and has genetic and autoimmune components. We genotyped 112 case–parent trios of European decent (confirmed by ancestry informative markers) using the immunoChip array, and performed association analyses with susceptibility to KD and intravenous immunoglobulin (IVIG) non-response. KD susceptibility was assessed using the transmission disequilibrium test, whereas IVIG non-response was evaluated using multivariable logistic regression analysis. We replicated single-nucleotide polymorphisms (SNPs) in three gene regions (FCGR, CD40/CDH22 and HLA-DQB2/HLA-DOB) that have been previously associated with KD and provide support to other findings of several novel SNPs in genes with a potential pathway in KD pathogenesis. SNP rs838143 in the 3′-untranslated region of the FUT1 gene (2.7 × 10−5) and rs9847915 in the intergenic region of LOC730109 | BRD7P2 (6.81 × 10−7) were the top hits for KD susceptibility in additive and dominant models, respectively. The top hits for IVIG responsiveness were rs1200332 in the intergenic region of BAZ1A | C14orf19 (1.4 × 10−4) and rs4889606 in the intron of the STX1B gene (6.95 × 10−5) in additive and dominant models, respectively. Our study suggests that genes and biological pathways involved in autoimmune diseases have an important role in the pathogenesis of KD and IVIG response mechanism.

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Acknowledgements

The parent study and this genetic sub-study conformed to the procedures for informed consent (parental permission) approved by institutional review boards at all sponsoring organizations and to human-experimentation guidelines set forth by the United States Department of Health and Human Services. We thank the participating patients and their parents. We also thank investigators (Neil E Bowles at Department of Pediatrics, University of Utah, Salt Lake City, UT; Hitendra Patel at Children’s Hospital of Oakland, Oakland, CA), pediatricians and staffs of the participating clinics. This study was supported by grants NHLBI-R21-HL90558 & The American Heart Association.

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Authors and Affiliations

  1. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

    A Shendre, H W Wiener & S Shrestha

  2. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

    D Zhi & A I Vazquez

  3. Department of Pediatrics, University of Washington, Seattle Children’s Research Institute, Seattle, WA, USA

    M A Portman

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  1. A Shendre
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Correspondence to S Shrestha.

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Shendre, A., Wiener, H., Zhi, D. et al. High-density genotyping of immune loci in Kawasaki disease and IVIG treatment response in European-American case–parent trio study. Genes Immun 15, 534–542 (2014). https://doi.org/10.1038/gene.2014.47

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