CASP3 gene single-nucleotide polymorphism (rs72689236) and Kawasaki disease in Taiwanese children

Abstract

,9,10Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. A study from Japan reported that G to A substitution of a single-nucleotide polymorphism (SNP) located in the 5¢-untranslated region of caspase 3 (CASP3) (rs72689236), which was associated with nuclear factor of activated T cell-mediated T-cell activation, is responsible for susceptibility to KD. This study was conducted to investigate whether the polymorphism of CASP3 is responsible for susceptibility and coronary artery lesion (CAL) formation in KD in the Taiwanese population. A total of 1092 subjects (341 KD patients and 751 controls) were investigated to identify an SNP of rs72689236 using Invader assays (Third Wave Technologies). Our data provided a borderline significant association between the genotypes and allele frequency of rs72689236 in control subjects and KD patients (P¼0.0535 under the dominant model; P¼0.0575 under the allelic model). The A allele of rs72689236 in KD patients and in patients with CAL and intravenous immunoglobulin resistance was seen in a higher frequency. Importantly, a significant association was obtained between rs72689236 and KD patients with aneurysm formation (P¼0.009, under the recessive model). The A allele of rs72689236 is very likely to be a risk allele in the development of aneurysm in patients with KD.

Genetic polymorphisms in Kawasaki disease

“…The CASP3 (rs72689236) is replicated in the KD patients in the Taiwanese population. Kuo et al provided further evidence that the A allele of rs72689236 is very likely to be a risk allele in the development of aneurysms in patients with KD [20] .…”

“…Interestingly, there are some genes associated with susceptibility to KD, but not CAL formation. We hypothesize that the genes responsible for susceptibility and CAL formation may be distinct [20,39,40] .…”

“…In the Asian population, we reported that monocytosis, eosinophilia, and eosinophilrelated Th2 immune response (especially, plasma level of IL-5) are associated with CAL formation and/or initial intravenous immunoglobulin (IVIG) treatment response [13][14][15][16] . Immunerelated genes, such as CTLA-4, CASP3 and ITPKC, have also been suggested to influence the susceptibility to and the clinical status of KD [14,15,[17][18][19][20][21] .…”

“…This therapy was within 10 d of illness and, if possible, within 7 d of illness. From a serial analysis of coronary artery lesions (n=341) in Chang Gung Memorial Hospital-Kaohsiung [20] , 35% of KD patients had dilatation during the acute phase, 17.2% had dilatation one month after disease onset, 10.2% still had dilatation at two months of follow-up, and 4% had persistent CAL for more than one year [39] .…”

“…For example, a number of genes have been reported to have significant associations with the susceptibility to KD in different populations. For instance, single nucleotide polymorphisms (SNPs) in the monocyte chemoattractant protein 1 (MCP-1) [29] , IL-10 [30][31][32] , CD40L [33] , IL-4 [26] , CASP3 [20,34] , IL-18 [35] , IL-1B [36] , HLA-E [37] , C-C chemokine receptor 5 (CCR5) [38] , and inositol 1, 4, 5-trisphosphate 3-kinase C (ITPKC) [21,39] have been reported to be associated with the development of KD. In early 2011, Shimizu et al [12] first reported that genetic polymorphisms of TGFB2, TGFBR2, and SMAD3 are associated with susceptibility to Kawasaki disease and the development of coronary artery lesions.…”