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 (FcγR) 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 FcγRs was assessed using pyrosequencing. We performed the transmission disequilibrium test to examine the association of GCN for FcγRs (FcγR2C, FcγR3A, and FcγR3B) with susceptibility and used logistic regression models to determine its association with IVIG treatment outcomes. Results: FcγR2C and FcγR3B GCN were significantly associated with KD susceptibility. IVIG response was associated with GCN variations of FcγR3B in Whites and FcγR2C in Hispanics, and gene risk score based on single nucleotide polymorphism and GCN in FcγRs were significantly different between IVIG responders and nonresponders among Whites. We found no significant associations between coronary artery disease and any of the FcγR copy numbers. Conclusion: GCN of FcγR2C and FcγR3B influences IVIG treatment response and predisposes individuals to KD, providing potential insights into understanding the mechanism of the FcγR gene family in the IVIG pathway. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.