| Autor: |
Kwon YC; Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea., Kim JJ; Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea., Yun SW; Department of Pediatrics, Chung-Ang University Hospital, Seoul, Korea., Yu JJ; Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea., Yoon KL; Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Seoul, Korea., Lee KY; Department of Pediatrics, The Catholic University of Korea, Daejeon St. Mary's Hospital, Daejeon, Korea., Kil HR; Department of Pediatrics, Chungnam National University Hospital, Daejeon, Korea., Kim GB; Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea., Han MK; Department of Pediatrics, University of Ulsan, Gangneung Asan Hospital, Gangneung, Korea., Song MS; Department of Pediatrics, Inje University Haeundae Paik Hospital, Busan, Korea., Lee HD; Department of Pediatrics, Pusan National University Hospital, Busan, Korea., Ha KS; Department of Pediatrics, Korea University Hospital, Seoul, Korea., Sohn S; Department of Pediatrics, Ewha Womans University Hospital, Seoul, Korea., Ebata R; Department of Pediatrics, Chiba-University Graduate School of Medicine, Chiba, Japan., Hamada H; Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan., Suzuki H; Department of Pediatrics, Wakayama Medical University, Wakayama, Japan., Ito K; Laboratory for Cardiovascular diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Onouchi Y; Laboratory for Cardiovascular diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Department of Public Health, Chiba University Graduate School of Medicine, Chiba, Japan., Hong YM; Department of Pediatrics, Ewha Womans University Hospital, Seoul, Korea., Jang GY; Department of Pediatrics, Korea University Hospital, Seoul, Korea., Lee JK; Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea. |
| Abstrakt: |
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. |
