Meta-analyses of the associations of genome-wide association study- linked gene loci with Kawasaki disease / 中华儿科杂志

ABSTRACT

<p><b>OBJECTIVE</b>Kawasaki disease (KD) is a common autoimmune vasculitis. It has been regarded as the leading cause of acquired heart disease in children. This study aimed to assess the relationship between genome-wide association study (GWAS)-linked gene loci and KD.</p><p><b>METHOD</b>By March of 2013, the published GWAS literatures of KD were retrieved from the databases including PubMed, MEDLINE, Web of Science, Cochrane Library, CNKI, VIP and Wanfang, and the gene loci associated with KD at genome-wide significance of P < 5.0×10(-8) were determined. For each of the gene loci, one single-nucleotide polymorphism (SNP) with strong association with KD was chosen for meta-analysis. Then the published case-control studies reporting the associations of the SNPs with KD were collected from English and Chinese databases with the same criteria. The Meta-analyses were conducted with RevMan 5.1 software after screening and evaluation.</p><p><b>RESULT</b>A total of 4 gene loci including FCGR2A, BLK, CD40 and HLA were observed having association with KD at genome-wide significance of P < 5.0×10(-8) in at least one GWAS. The risk alleles of the SNPs in the gene loci were all more common in patients with KD relative to controls in the systematic reviews with 8, 4, 6 and 4 extracted case-control studies, respectively[ FCGR2A rs1801274 P < 0.001, OR = 1.40, 95% CI (1.30, 1.51); BLK rs2254546 P < 0.001, OR = 1.69, 95% CI (1.52, 1.88); CD40 rs4813003 P < 0.001, OR = 1.31, 95% CI (1.22, 1.41); HLA rs2857151 P < 0.001, OR = 1.41, 95% CI (1.27, 1.57)]. The significant publication bias was not observed in the meta-analyses.</p><p><b>CONCLUSION</b>Our results confirmed the overall association of the 4 gene loci with KD in observed populations, together with the consistent presence of the relationship between BLK or HLA and KD in the populations, suggesting that it is hopeful to find the genetic marker combination predicting the risk of KD, the formation of secondary coronary artery lesions and the resistance of intravenous immunoglobulin, by further seeking the function SNPs of the gene loci and investigating the effect on the important clinical phenotypes of KD.</p>