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.
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.
Authors: David L Morris; Amy L Roberts; Abigail S Witherden; Ruth Tarzi; Paula Barros; John C Whittaker; Terence H Cook; Timothy J Aitman; Timothy J Vyse Journal: Eur J Hum Genet Date: 2010-05-05 Impact factor: 4.246
Authors: Sadeep Shrestha; Howard W Wiener; Aaron K Olson; Jeffrey C Edberg; Neil E Bowles; Hitendra Patel; Michael A Portman Journal: J Allergy Clin Immunol Date: 2011-05-20 Impact factor: 10.793
Authors: Nina P Paynter; Daniel I Chasman; Guillaume Paré; Julie E Buring; Nancy R Cook; Joseph P Miletich; Paul M Ridker Journal: JAMA Date: 2010-02-17 Impact factor: 56.272
Authors: Michael A Portman; Aaron Olson; Brian Soriano; Nagib Dahdah; Richard Williams; Edward Kirkpatrick Journal: Am Heart J Date: 2011-03 Impact factor: 4.749
Authors: Willemijn B Breunis; Edwin van Mirre; Judy Geissler; Nadja Laddach; Gertjan Wolbink; Ellen van der Schoot; Masja de Haas; Martin de Boer; Dirk Roos; Taco W Kuijpers Journal: Hum Mutat Date: 2009-05 Impact factor: 4.878
Authors: Cushla McKinney; Manuela Fanciulli; Marilyn E Merriman; Amanda Phipps-Green; Behrooz Z Alizadeh; Bobby P C Koeleman; Nicola Dalbeth; Peter J Gow; Andrew A Harrison; John Highton; Peter B Jones; Lisa K Stamp; Sophia Steer; Pilar Barrera; Marieke J H Coenen; Barbara Franke; Piet L C M van Riel; Tim J Vyse; Tim J Aitman; Timothy R D J Radstake; Tony R Merriman Journal: Ann Rheum Dis Date: 2010-05-14 Impact factor: 19.103
Authors: Lisa C Willcocks; Paul A Lyons; Menna R Clatworthy; James I Robinson; Wanling Yang; Stephen A Newland; Vincent Plagnol; Naomi N McGovern; Alison M Condliffe; Edwin R Chilvers; Dwomoa Adu; Elaine C Jolly; Richard Watts; Yu Lung Lau; Ann W Morgan; Gerard Nash; Kenneth G C Smith Journal: J Exp Med Date: 2008-06-16 Impact factor: 14.307
Authors: Hea-Ji Kim; Jae-Jung Kim; Sin Weon Yun; Jeong Jin Yu; Kyung Lim Yoon; Kyung-Yil Lee; Hong-Ryang Kil; Gi Beom Kim; Myung-Ki Han; Min Seob Song; Hyoung Doo Lee; Kee Soo Ha; Young Mi Hong; Gi Young Jang; Jong-Keuk Lee Journal: J Hum Genet Date: 2020-01-22 Impact factor: 3.172
Authors: Jacqueline Kerr; Isabella Quinti; Martha Eibl; Helen Chapel; Peter J Späth; W A Carrock Sewell; Abdulgabar Salama; Ivo N van Schaik; Taco W Kuijpers; Hans-Hartmut Peter Journal: Front Immunol Date: 2014-12-12 Impact factor: 7.561
Authors: Marlena Typiak; Krzysztof Rębała; Agnieszka Haraś; Monika Skotarczak; Jan Marek Słomiński; Anna Dubaniewicz Journal: PLoS One Date: 2017-05-04 Impact factor: 3.240