Journal article
Pharmacogenomics of coronary artery response to intravenous gamma globulin in kawasaki disease
Npj genomic medicine, Vol.9(1), pp.34-10
05/30/2024
DOI: 10.1038/s41525-024-00419-7
PMCID: PMC11139870
PMID: 38816462
Abstract
Kawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that can result in acute vasculitis. The mechanism of coronary artery aneurysms (CAA) in KD despite intravenous gamma globulin (IVIG) treatment is not known. We performed a Whole Genome Sequencing (WGS) association analysis in a racially diverse cohort of KD patients treated with IVIG, both using AHA guidelines. We defined coronary aneurysm (CAA) (N = 234) as coronary z >= 2.5 and large coronary aneurysm (CAA/L) (N = 92) as z >= 5.0. We conducted logistic regression models to examine the association of genetic variants with CAA/L during acute KD and with persistence >6 weeks using an additive model between cases and 238 controls with no CAA. We adjusted for age, gender and three principal components of genetic ancestry. The top significant variants associated with CAA/L were in the intergenic regions (rs62154092 p < 6.32E-08 most significant). Variants in SMAT4, LOC100127, PTPRD, TCAF2 and KLRC2 were the most significant non-intergenic SNPs. Functional mapping and annotation (FUMA) analysis identified 12 genomic risk loci with eQTL or chromatin interactions mapped to 48 genes. Of these NDUFA5 has been implicated in KD CAA and MICU and ZMAT4 has potential functional implications. Genetic risk score using these 12 genomic risk loci yielded an area under the receiver operating characteristic curve (AUC) of 0.86. This pharmacogenomics study provides insights into the pathogenesis of CAA/L in IVIG-treated KD and shows that genomics can help define the cause of CAA/L to guide management and improve risk stratification of KD patients.
Details
- Title: Subtitle
- Pharmacogenomics of coronary artery response to intravenous gamma globulin in kawasaki disease
- Creators
- Sadeep Shrestha - University of Alabama at BirminghamHoward W. Wiener - University of Alabama at BirminghamSabrina Chowdhury - University of Alabama at BirminghamHidemi Kajimoto - University of WashingtonVinodh Srinivasasainagendra - University of Alabama at BirminghamOlga A. Mamaeva - University of Alabama at BirminghamUjval N. Brahmbhatt - University of Alabama at BirminghamDolena Ledee - Seattle Children's HospitalYung R. Lau - University of Alabama at BirminghamLuz A. Padilla - University of Alabama at BirminghamJake Y. Chen - University of Alabama at BirminghamNagib Dahdah - Université de MontréalHemant K. Tiwari - University of Alabama at BirminghamMichael A. Portman - Seattle Children's Hospital
- Resource Type
- Journal article
- Publication Details
- Npj genomic medicine, Vol.9(1), pp.34-10
- DOI
- 10.1038/s41525-024-00419-7
- PMID
- 38816462
- PMCID
- PMC11139870
- NLM abbreviation
- NPJ Genom Med
- ISSN
- 2056-7944
- eISSN
- 2056-7944
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 10
- Grant note
- NHLBI-1R01HL146130 / United States Department of Health and Human Services U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 05/30/2024
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics
- Record Identifier
- 9984961112802771
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