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

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 perf...

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Published in:PloS one 2017-09, Vol.12 (9), p.e0184248-e0184248
Main Authors: Kwon, Young-Chang, Kim, Jae-Jung, Yun, Sin Weon, Yu, Jeong Jin, Yoon, Kyung Lim, Lee, Kyung-Yil, Kil, Hong-Ryang, Kim, Gi Beom, Han, Myung-Ki, Song, Min Seob, Lee, Hyoung Doo, Ha, Kee-Soo, Sohn, Sejung, Ebata, Ryota, Hamada, Hiromichi, Suzuki, Hiroyuki, Ito, Kaoru, Onouchi, Yoshihiro, Hong, Young Mi, Jang, Gi Young, Lee, Jong-Keuk
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Substitution
Arthritis
Asian Continental Ancestry Group - genetics
Autoimmune diseases
Biology and Life Sciences
Case-Control Studies
Children
Codon
Consortia
Coronary artery
Fc receptors
Female
Females
Gender
Gender aspects
Genetic Association Studies
Genetic Predisposition to Disease
Genome-wide association studies
Genomes
Genotype
Health sciences
Hospitals
Humans
Interleukin 1
Japan
Kawasaki disease
Laboratories
Life sciences
Male
Males
Medicine
Medicine and Health Sciences
Meta-analysis
Mucocutaneous lymph node syndrome
Mucocutaneous Lymph Node Syndrome - genetics
Odds Ratio
Pathogenesis
Pediatrics
People and Places
Physical Sciences
Polymorphism
Polymorphism, Single Nucleotide
Population
Receptors, IgG - genetics
Receptors, Interleukin-17 - genetics
Republic of Korea
Research and Analysis Methods
Semaphorins - genetics
Sex
Sex differences
Sex Factors
Single-nucleotide polymorphism
Stroke
Systemic vasculitis
Womens health
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0184248