Combined analysis of genome-wide-linked susceptibility loci to Kawasaki disease in Han Chinese
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ORIGINAL INVESTIGATION
Combined analysis of genome-wide-linked susceptibility loci to Kawasaki disease in Han Chinese Yuanlong Yan • Yongyi Ma • Yunqiang Liu • Hongde Hu • Ying Shen • Sizhong Zhang • Yongxing Ma • Dachang Tao • Qing Wu • Qian Peng • Yuan Yang
Received: 5 December 2012 / Accepted: 16 February 2013 / Published online: 1 March 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Abstract Kawasaki disease (KD) is a dominant cause of acquired heart disease in children due to frequent complicating coronary artery lesions (CALs). Genome-wide association study and linkage analysis have recently identified 6 susceptibility loci at genome-wide significance of P \ 5.0 9 10-8 in subjects of Japanese, Taiwanese and European. In present study, we analysed the variants of 6 single nucleotide polymorphisms (SNPs) in the genetic loci to investigate their potential effect on KD susceptibility and outcomes in Han Chinese population. As a result, the risk alleles of rs1801274 and rs2254546 were observed significant effect on KD with higher frequencies in 358 patients than those in 815 controls. The significant role of rs1801274, rs2857151 and rs2254546 in KD was found in the multi-variable logistic regression analysis of the SNPs. Y. L. Yan and Y. Y. Ma contributed equally to this study and share first authorship.
Electronic supplementary material The online version of this article (doi:10.1007/s00439-013-1279-2) contains supplementary material, which is available to authorized users. Y. Yan Y. Ma Y. Liu Y. Shen S. Zhang Y. Ma D. Tao Y. Yang (&) Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China e-mail: [email protected] H. Hu Department of Cardiovascular Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China Q. Wu Q. Peng (&) Department of Pediatrics, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan, China e-mail: [email protected]
Two 2-locus and one 3-locus combinations of the SNPs showed significant effect on KD with stronger association with KD relative to comparable single SNP or 2-locus combinations. Significant susceptibility to CALs was found in KD patients with high-risk genotypes at both rs1801274 and rs2857151. The meta-analyses first revealed significant risk for CALs in KD patients carrying risk allele of rs11340705, and the association of rs28493229 with KD was not observed in the Han Chinese. In conclusion, the findings demonstrated that 5 of the 6 genetic loci influence the risk for KD and 3 of them may be involved in secondary CALs formation in Han Chinese. The additive effects of 3 multi-locus combinations on KD/CALs imply that some loci may participate together in certain unknown gene networks related to KD/CALs. Further function studies of the genetic loci are helpful for better understanding the pathophysiology of KD.
Introduction Kawasaki disease (KD) is an acute, self-limited vasculitis that primarily affects chil
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