Journal
PHARMACOGENETICS AND GENOMICS
Volume 23, Issue 9, Pages 455-462Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FPC.0b013e328363686e
Keywords
copy number variation; Fc gamma R; genetic risk; intravenous immunoglobulin; Kawasaki disease
Funding
- American Heart Association
- Thrasher Foundation Research
- [NHLBI-R21-HL90558]
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Objective Kawasaki disease (KD), response to intravenous immunoglobulin (IVIG) therapy, and associated coronary artery disease progression have been associated with genetic polymorphisms in Fc gamma receptor (Fc gamma R) genes. However, it is not known whether the existing gene copy number (GCN) variability relates to KD treatment response, susceptibility, or associated sequelae.Methods The copy number of individuals with KD (n=510) and their family members (n=808) for three variable Fc gamma Rs was assessed using pyrosequencing. We performed the transmission disequilibrium test to examine the association of GCN for Fc gamma Rs (Fc gamma R2C, Fc gamma R3A, and Fc gamma R3B) with susceptibility and used logistic regression models to determine its association with IVIG treatment outcomes.Results Fc gamma R2C and Fc gamma R3B GCN were significantly associated with KD susceptibility. IVIG response was associated with GCN variations of Fc gamma R3B in Whites and Fc gamma R2C in Hispanics, and gene risk score based on single nucleotide polymorphism and GCN in Fc gamma Rs were significantly different between IVIG responders and nonresponders among Whites. We found no significant associations between coronary artery disease and any of the Fc gamma R copy numbers.Conclusion GCN of Fc gamma R2C and Fc gamma R3B influences IVIG treatment response and predisposes individuals to KD, providing potential insights into understanding the mechanism of the Fc gamma R gene family in the IVIG pathway.
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