Kawasaki disease (KD) is the most common cause of paediatric acquired heart disease, which may be attributed to the combined effects of infection, immunological response, and genetic susceptibility. The most severe complication in KD is acute coronary artery lesions (CALs), including myocardial infarction and coronary artery aneurysms. Mounting evidence indicates that adhesion molecules and chemokines play an important role in inflammation and cardiovascular disease on basis of pathogenesis. Thus, this study aimed to investigate the association of seven single nucleotide polymorphisms (SNPs) of adhesion molecules and chemokines (P-selectin 290G>A, PSGL-1 62G>A, MCP-1 -2518A>G, SDF-1 -801G>A, PECAM-1 L125V, PECAM-1 S563N and PECAM-1 R670G) with the risk of KD, sequelae of CALs and initial intravenous immunoglobulin (IVIG) treatment failure. A total of 301 KD children (185 without acute and chronic CALs, 81 with acute but without chronic CALs, and 33 with acute and chronic CALs) and 246 sex-matched healthy controls were recruited in the case-control study. In addition, 166 cases from the above KD children and 332 parents were recruited to carry out case-parent trio study. We found that PECAM-1 3 SNPs polymorphisms were not associated with above several risks, except for CALs in chronic stage. As compared with non-Leu-Ser-Arg haplotype, Leu-Ser-Arg haplotype was associated with a significant increased risk for CALs in the chronic stage (AOR 2.50, 95% CI 1.05-6.00, P=0.039). Analyses based on the diplotypes of PECAM-1 also showed that Leu-Ser-Arg allele had a significant increased risk of CALs in chronic stage in dominant manner (AOR 2.98, 95% CI 1.15-7.72, P=0.024). In addition, carriers of Leu-Ser-Arg allele had significant increased counts of platelet (¡Ñ1000/Cumm) (672.6¡Ó207.6 versus 563.1¡Ó196.8; P=0.027) within 10 days of diagnosis of KD. Moreover, we also found a significant correlation between each SNP and polymorphonuclear neutrophil counts by genotype analysis. As for other genes, there were no markedly different outcomes regardless of the risk of KD, sequelae of CALs or initial IVIG treatment failure. In conclusion, the haplotype Leu-Ser-Arg of PECAM-1 is a genetic marker of susceptibility to sequelae of chronic CALs for KD patients. However, the role of PECAM-1 SNPs in CALs formation in the chronic stage in KD patients still needs further evaluation.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0827110-203936 |
| Date | 27 August 2010 |
| Creators | Huang, Sing-chih |
| Contributors | Yow-ling Shiue, Luo-ping Ger, Kai-sheng Hsieh |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0827110-203936 |
| Rights | not_available, Copyright information available at source archive |
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