ITPKC Single Nucleotide Polymorphism Associated with the Kawasaki Disease in a Taiwanese Population

Kuo, Ho‐Chang; Yang, Kuender D.; Juo, Suh‐Hang Hank; Liang, Chi-Di; Chen, Wei-Chiao; Wang, Yu-Shiuan; Lee, Chih‐Hung; Hsi, Edward; Yu, Hong‐Ren; Woon, Peng-Yeong; Lin, I-Chun; Huang, Chien-Fu; Hwang, Daw-Yang; Lee, Chiu-Ping; Lin, Li-Yan; Chang, Wei Pin; Chang, Wei‐Chiao

doi:10.1371/journal.pone.0017370

Cited by 89 publications

(71 citation statements)

References 22 publications

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“…KD may lead to formation of coronary artery aneurysms and to ischemic heart disease, myocardial infarction and sudden death (Hata and Onouchi, 2009). The link between this ITPKC polymorphism and KD (or resistance to KD treatment) was confirmed in other studies, but others failed to reproduce these results and no association of the ITPKC locus with KD was detected (Burgner et al, 2009;Khor et al, 2011;Kuo et al, 2011;Lin et al, 2011;Onouchi et al, 2013;Peng et al, 2012).…”

Section: Introductionmentioning

confidence: 76%

Specific expression and function of inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) in wild type and knock-out mice

Scoumanne

Molina-Ortíz

Monteyne

et al. 2016

Advances in Biological Regulation

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a b s t r a c tInositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is the last identified member of the inositol 1,4,5-trisphosphate 3-kinases family which phosphorylates inositol 1,4,5-trisphosphate into inositol 1,3,4,5-tetrakisphosphate. Although expression and function of the two other family members ITPKA and ITPKB are rather well characterized, similar information is lacking for ITPKC. Here, we first defined the expression of Itpkc mRNA and protein in mouse tissues and cells using in situ hybridization and new antibodies. Surprisingly, we found that cells positive for ITPKC in the studied tissues express either a multicilium (tracheal and bronchial epithelia, brain ependymal cells), microvilli forming a brush border (small and large intestine, and kidney proximal tubule cells) or a flagellum (spermatozoa), suggesting a role for ITPKC either in the development or the function of these specialized cellular structures. Given this surprising expression, we then analyzed ITPKC function in multiciliated tracheal epithelial cells and sperm cells using our Itpkc knock-out mouse model. Unfortunately, no significant difference was observed between control and mutant mice for any of the parameters tested, leaving the exact in vivo function of this third Ins(1,4,5)P3 3-kinase still open.

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Section: Introductionmentioning

confidence: 76%

Specific expression and function of inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) in wild type and knock-out mice

Scoumanne

Molina-Ortíz

Monteyne

et al. 2016

Advances in Biological Regulation

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“…The results from a study by Lin et al [63] in another independent medical center in Taipei indicated that the C allele of rs28493229 is associated with KD susceptibility. Recently, new results using meta-analysis showed that the rs28493229 SNP of ITPKC is associated with the susceptibility to KD in the Taiwanese population [39] . Regarding to the controversial results obtained for ITPKC genetic association studies in the Taiwanese population, we attribute them to population migration, due to the increase in genetic diversity between cities in the south or north of Taiwan [39] .…”

Section: Genetic Polymorphisms Of the Itpkc Signaling Pathway In Patimentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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] .…”

Section: Introductionmentioning

confidence: 99%

“…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] .…”

Section: Introductionmentioning

confidence: 99%

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Genetic polymorphisms in Kawasaki disease

Kuo

Chang²

2011

Acta Pharmacol Sin

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Kawasaki disease (KD) is an acute febrile systemic vasculitis, and the cause of KD is not well understood. It is likely due to multiple interactions between genes and environmental factors. The development of genetic association and genome-wide association studies (GWAS) has opened an avenue to better understanding the molecular mechanisms underlying KD. A novel ITPKC signaling pathway was recently found to be responsible for the susceptibility to KD. Furthermore, the GWAS demonstrated the functionally related susceptibility loci for KD in the Caucasian population. In the last decade, the identification of several genomic regions linked to the pathogenesis of KD has made a major breakthrough in understanding the genetics of KD. This review will focus on genetic polymorphisms associated with KD and describe some of the possible clinical implications and molecular mechanisms that can be used to explain how genetic variants regulate the pathogenesis in KD.

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Identification of an Association Between Genomic Hypomethylation of FCGR2A and Susceptibility to Kawasaki Disease and Intravenous Immunoglobulin Resistance by DNA Methylation Array

Kuo

Chang

Kuo

et al. 2015

Arthritis & Rheumatology

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Objective. Kawasaki disease (KD) is characterized by systemic vasculitis, and it is the most common acquired heart disease in children. However, the etiology and immunopathogenesis of KD are still unclear. A genome-wide association study (GWAS) identified polymorphisms in CD40, BLK, and FCGR2A as the susceptibility genes for KD. No epigenetic array studies of KD have previously been published. This study was undertaken to investigate differences in DNA methylation in patients with KD as compared to controls.Methods. The HumanMethylation27 BeadChip (Illumina) was used to survey the differences in DNA methylation between KD patients and controls. DNA methylation array validation was performed in a separate cohort by pyrosequencing assay and reporter gene assays. Messenger RNA (mRNA) expression was determined, and the association of methylation with response to intravenous immunoglobulin (IVIG) treatment was analyzed.Results. HumanMethylation27 BeadChip assay showed a 15% difference in methylation of 10 genes between KD patients and controls. The FCGR2A cg24422489 group, which was recently reported to be associated with KD susceptibility in a GWAS, had significant hypomethylation of 15.54% less in the KD group than in the control group. Validation of FCGR2A methylation in another cohort also showed significant hypomethylation in the KD group (5 of 5 CpG sites [P < 0.01]; n ‫؍‬ 43 in the KD group and n ‫؍‬ 55 in the control group). KD patients with IVIG resistance showed hypomethylation of 5 CpG sites (P < 0.05). FCGR2A mRNA expression was significantly increased in patients in the acute stage of KD compared to controls. Reporter gene assays indicated that the CpG sites of the FCGR2A promoter region were sufficient to modulate gene expression.Conclusion. This is the first study to examine the DNA methylation array in KD and identify a role of hypomethylation of FCGR2A in susceptibility to KD and IVIG resistance.Kawasaki disease (KD) is an acute febrile systemic vasculitis first described by Kawasaki et al (1) in English in 1974. The most serious complication of KD is the formation of coronary artery lesions, including myocardial infarction, coronary artery fistula, coronary artery dilatation, and aneurysm (2). In developed countries, it is the leading cause of acquired heart disease in children; however, its etiology remains unknown (3-6). KD mainly affects children younger than 5 years of age, especially those in Asian countries, but its incidence has increased worldwide.

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ITPKC Single Nucleotide Polymorphism Associated with the Kawasaki Disease in a Taiwanese Population

Cited by 89 publications

References 22 publications

Specific expression and function of inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) in wild type and knock-out mice

Specific expression and function of inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) in wild type and knock-out mice

Genetic polymorphisms in Kawasaki disease

Identification of an Association Between Genomic Hypomethylation of FCGR2A and Susceptibility to Kawasaki Disease and Intravenous Immunoglobulin Resistance by DNA Methylation Array

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