Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease.
Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease.
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DOI：
10.1371/journal.pone.0184248
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Korean Kawasaki Disease Genetics Consortium
中科院分区：
文献类型：
--
作者：
Kwon YC;Kim JJ;Yun SW;Yu JJ;Yoon KL;Lee KY;Kil HR;Kim GB;Han MK;Song MS;Lee HD;Ha KS;Sohn S;Ebata R;Hamada H;Suzuki H;Ito K;Onouchi Y;Hong YM;Jang GY;Lee JK;Korean Kawasaki Disease Genetics Consortium
川崎是一种急性全身性血管炎，在某些儿童中可能导致冠状动脉瘤。KD在男性中的发生频率约为女性的1.5倍。为了确定儿童KD发病机制中涉及的性别特异性遗传变异，我们使用Illumina HumanOmni 1-Quad BeadChip数据（249例病例和1，000例对照）进行了性别分层全基因组关联研究（GWAS），并在独立样本集（671例病例和3，553例对照）中对34个性别特异性候选SNP进行了复制研究。在三种常见变异中检测到男性特异性关联：FCGR 2A中的rs 1801274 [比值比（OR）= 1.40，P = 9.31 × 10−5]，SEMA 6A中的rs 12516652（OR = 1.87，P = 3.12 × 10−4），以及IL 17 REL附近的rs 5771303（OR = 1.57，P = 2.53 × 10−5）。FCGR 2A的男性特异性相关性，而不是SEMA 6A和IL 17 REL，也在日本人群中复制（男性OR = 1.74，P = 1.04 × 10−4 vs.女性OR = 1.22，P = 0.191）。在一项包含1,461例病例和5,302例对照的荟萃分析中，KD与FCGR 2A中非同义SNP rs 1801274（p.His167Arg，之前被指定为p.His131Arg）的关联在男性中得到证实（OR = 1.48，P = 1.43 × 10−7），但在女性中没有（OR = 1.17，P = 0.055）。目前的研究表明，p.His167Arg，KD相关的FCGR 2A变异，作为一个易感基因，在男性中只。总体而言，KD中与FCGR 2A相关的性别差异为KD易感性提供了新的见解。
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.
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影响因子：
7.8
作者：
Giefing-Kröll C;Berger P;Lepperdinger G;Grubeck-Loebenstein B
通讯作者：
Grubeck-Loebenstein B
影响因子：
7.7
作者：
GREEN, MS
通讯作者：
GREEN, MS
影响因子：
3.6
作者：
Holman, Robert C.;Belay, Ermias D.;Schonberger, Lawrence B.
通讯作者：
Schonberger, Lawrence B.
影响因子：
5.3
作者：
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通讯作者：
Lee, Jong-Keuk
DOI：
10.1002/aur.1227
发表时间：
2012-04
期刊：
Autism research : official journal of the International Society for Autism Research
影响因子：
--
作者：
Becker KG
通讯作者：
Becker KG