Pharmacogenomics of coronary artery response to intravenous gamma globulin in kawasaki disease

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) associa...

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Veröffentlicht in:Npj genomic medicine 2024-05, Vol.9 (1), p.34-10, Article 34
Hauptverfasser: Shrestha, Sadeep, Wiener, Howard W., Chowdhury, Sabrina, Kajimoto, Hidemi, Srinivasasainagendra, Vinodh, Mamaeva, Olga A., Brahmbhatt, Ujval N., Ledee, Dolena, Lau, Yung R., Padilla, Luz A., Chen, Jake Y., Dahdah, Nagib, Tiwari, Hemant K., Portman, Michael A.
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Sprache:eng
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Zusammenfassung: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  
ISSN:2056-7944
2056-7944
DOI:10.1038/s41525-024-00419-7