Association of an IGHV3-66 gene variant with Kawasaki disease.
СтатьяМетаанализНазвание и аннотация: Перевод в очереди
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Johnson Todd A, Mashimo Yoichi, Wu Jer-Yuarn, Yoon Dankyu, Hata Akira, Kubo Michiaki, Takahashi Atsushi, Tsunoda Tatsuhiko, Ozaki Kouichi, Tanaka Toshihiro, Ito Kaoru, Suzuki Hiroyuki, Hamada Hiromichi, Kobayashi Tohru, Hara Toshiro, Chen Chien-Hsiun, Lee Yi-Ching, Liu Yi-Min, Chang Li-Ching, Chang Chun-Ping, Hong Young-Mi, Jang Gi-Young, Yun Sin-Weon, Yu Jeong-Jin, Lee Kyung-Yil, Kim Jae-Jung, Park Taesung, Korean Kawasaki Disease Genetics Consortium, Taiwan Kawasaki Disease Genetics Consortium, Taiwan Pediatric ID Alliance, Japan Kawasaki Disease Genome Consortium, Lee Jong-Keuk, Chen Yuan-Tsong, Onouchi Yoshihiro
Аннотация
In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10-9). Investigation of nonsynonymous SNVs of the IGHV cluster in 9335 Japanese subjects identified the C allele of rs6423677, located in IGHV3-66, as the most significant reproducible association (OR = 1.25, P = 6.8 × 10-10 in 3603 cases and 5731 controls). We observed highly skewed allelic usage of IGHV3-66, wherein the rs6423677 A allele was nearly abolished in the transcripts in peripheral blood mononuclear cells of both KD patients and healthy adults. Association of the high-expression allele with KD strongly indicates some active roles of B-cells or endogenous immunoglobulins in the disease pathogenesis. Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD.