Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease.

• Main Authors: Young-Chang Kwon, 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, Sejung Sohn, Ryota Ebata, Hiromichi Hamada, Hiroyuki Suzuki, Kaoru Ito, Yoshihiro Onouchi, Young Mi Hong, Gi Young Jang, Jong-Keuk Lee, Korean Kawasaki Disease Genetics Consortium
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2017-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC5590908?pdf=render

Kawasaki disease (KD) is an acute systemic vasculitis that can potentially cause coronary artery aneurysms in some children. KD occurs approximately 1.5 times more frequently in males than in females. To identify sex-specific genetic variants that are involved in KD pathogenesis in children, we performed a sex-stratified genome-wide association study (GWAS), using the Illumina HumanOmni1-Quad BeadChip data (249 cases and 1,000 controls) and a replication study for the 34 sex-specific candidate SNPs in an independent sample set (671 cases and 3,553 controls). Male-specific associations were detected in three common variants: rs1801274 in FCGR2A [odds ratio (OR) = 1.40, P = 9.31 × 10-5], rs12516652 in SEMA6A (OR = 1.87, P = 3.12 × 10-4), and rs5771303 near IL17REL (OR = 1.57, P = 2.53 × 10-5). The male-specific association of FCGR2A, but not SEMA6A and IL17REL, was also replicated in a Japanese population (OR = 1.74, P = 1.04 × 10-4 in males vs. OR = 1.22, P = 0.191 in females). In a meta-analysis with 1,461 cases and 5,302 controls, a very strong association of KD with the nonsynonymous SNP rs1801274 (p.His167Arg, previously assigned as p.His131Arg) in FCGR2A was confirmed in males (OR = 1.48, P = 1.43 × 10-7), but not in the females (OR = 1.17, P = 0.055). The present study demonstrates that p.His167Arg, a KD-associated FCGR2A variant, acts as a susceptibility gene in males only. Overall, the gender differences associated with FCGR2A in KD provide a new insight into KD susceptibility.