Chiu-Ping Lee

Chang Gung Memorial Hospital, T’ai-pei, Taipei, Taiwan

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Publications (8)20.07 Total impact

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    ABSTRACT: Background: 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 is still unclear. Genome-wide association study (GWAS) identified polymorphisms in CD40, BLK, and FCGR2A as the susceptibility genes for KD. There were no epigenetic array studies about KD until now, and this study was conducted to investigate DNA methylation difference in KD. Methods: The HumanMethylation27 BeadChip (Illumina) was used to survey the difference in DNA methylation between KD and control groups. Validation from another cohort of DNA methylation array was performed by pyrosequencing assay and reporter gene assays. The expression levels were determined by mRNA expression and the association was analyzed with the response to intravenous immunoglobulin (IVIG) treatment. Results: Ten genes showed 15% methylation difference between KD and control through HumanMethylation27 BeadChip assay. The FCGR2A (cg24422489) group, which was recently reported to be associated with KD susceptibility from GWAS, had a significant hypomethylation of 15.54% less than control group. Validation of FCGR2A methylation from another cohort also showed significant hypomethylation in KD group (5/5 CpG site, p < 0.01, N = 43 of KD group and N = 55 of control). KD with IVIG resistance showed hypomethylation in 5 CpG sites of (p < 0.05). FCGR2A mRNA expression levels showed significant increase in the acute stage of KD when compared to control group. Reporter gene assays indicated that the regions CpG sites of FCGR2A promoter region were sufficient to modulate gene expression. Conclusion: This is the first study dealing with DNA methylation array in KD and identifying hypomethylation of FCGR2A in the susceptibility of KD and IVIG resistance. This article is protected by copyright. All rights reserved. Copyright © 2014 American College of Rheumatology.
    Arthritis & rheumatology (Hoboken, N.J.). 12/2014;
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    ABSTRACT: To determine whether 3 biomarkers, L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA), can predict outcomes in patients with Kawasaki disease (KD).
    The Journal of pediatrics. 05/2014;
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    ABSTRACT: Background:Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. TARC/CCL17 is one of Th2 chemokine and has been suggested as a candidate gene for conferring susceptibility to Th2 associated with allergy diseases. This study examined the correlation gene polymorphisms and plasma levels of TARC/CCL17 (Thymus and activation-regulated chemokine/chemokine ligand 17) in the patients with KD and the outcomes of KD.Methods:A total of 381 KD patients and 564 controls were subjected to determination of 5 tagging single nucleotide polymorphisms (tSNPs) of TARC/CCL17. In addition, plasma TARC/CCL17 levels were measured by ELISA.Results:Polymorphisms of TARC/CCL17 were significantly different between normal children and patients with KD. The A allele of rs4784805 with better intravenous immunoglobulin treatment response to KD. Furthermore, plasma TARC/CCL17 levels were higher in KD patients than in controls before intravenous immunoglobulin (IVIG) treatment. After IVIG treatment, plasma TARC/CCL17 levels decreased significantly.Conclusions:This study provides the first evidence supporting the association between TARC/CCL17 polymorphisms, susceptibility of KD and IVIG responses in KD patients.Pediatric Research (2013); doi:10.1038/pr.2013.134.
    Pediatric Research 08/2013; · 2.67 Impact Factor
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    ABSTRACT: Kawasaki disease (KD) is a systemic febrile vasculitis complicated by coronary artery lesions (CAL). Anemia is common in patients with KD and is associated with a prolonged duration of active inflammation. Hepcidin is a central modulator of inflammation-associated anemia, acting via control of iron absorption and a direct inhibitory effect on erythropoiesis. The aims of this study were to investigate the role of inflammation-induced hepcidin in the development of anemia, the occurrence of CAL formation, and IVIG treatment response in patients with KD. Eighty-six KD patients and 30 febrile controls were enrolled. Levels of interleukin (IL)-6 and serum hepcidin were measured in sera by enzyme-linked immunosorbent assay. Hemoglobin and serum iron levels were also measured. Hemoglobin and iron levels were lower in KD patients than in controls (p < 0.001 and p = 0.009, respectively). Serum hepcidin and IL-6 levels were higher in KD patients than in controls (both p < 0.001) before intravenous immunoglobulin (IVIG) treatment. After IVIG treatment, serum hepcidin, IL-6, and hemoglobin levels decreased significantly (all p < 0.001). In addition, the serum hepcidin levels before IVIG treatment were negatively correlated with hemoglobin levels after IVIG treatment (R = -0.188, p = 0.046) and positively correlated with the changes of hemoglobin levels after IVIG treatment (R = 0.269, p = 0.015). Furthermore, serum hepcidin levels were negatively correlated with serum iron levels (R = -0.412, p = 0.002), which were positively correlated with hemoglobin levels (R = 0.210, p = 0.045). Additionally, the change of hepcidin levels was associated with IVIG treatment response and the occurrence of CAL formation. Inappropriately raised hepcidin levels impair iron metabolism and are associated with decreased hemoglobin levels in KD patients. Inflammation-induced hepcidin is associated with the development of anemia and disease outcomes in patients with KD.
    Journal of Clinical Immunology 03/2012; 32(4):746-52. · 3.38 Impact Factor
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    ABSTRACT: the C-type lectin DC-SIGN (CD209) is known to be the major dengue receptor on human dendritic cells, and a single nucleotide polymorphism (SNP) in the promoter region of CD209 (-336 A/G; rs4804803) is susceptible to many infectious diseases. We reason that variations in the DC-SIGN gene might have a broad influence on viral replication and host immune responses. we studied whether the rs4804803 SNP was associated with a susceptibility to dengue fever (DF) and/or dengue hemorrhagic fever (DHF) through genotyping analysis in a Taiwanese cohort. We generated monocyte-derived dendritic cells (MDDCs) from individuals with AA or AG genotype of rs4804803 to study the viral replication and immune responses for functional validation. A total of 574 DNA samples were genotyped, including 176 DF, 135 DHF, 143 other non-dengue febrile illnesses (OFI) and 120 population controls. A strong association between GG/AG genotypes of rs4804803 and risk of DHF was found when compared among DF, OFI and controls (p = 0.004, 3×10(-5) and 0.001, respectively). The AA genotype was associated with protection against dengue infection compared with OFI and controls (p = 0.002 and 0.020, respectively). Moreover, MDDCs from individuals with AG genotype with a higher cell surface DC-SIGN expression had a significantly higher TNFα, IL-12p40, and IP-10 production than those with AA genotype in response to dengue infection. However, the viral replication in MDDCs with AG genotype was significantly lower than those with AA genotype. With both genotypes, MDDCs revealed an increase in viral replication following the addition of anti-IP-10 neutralizing antibody. the rs4804803 SNP in the CD209 promoter contributed to susceptibility to dengue infection and complication of DHF. This SNP with AG genotype affects the cell surface DC-SIGN expression related to immune augmentation and less viral replication.
    PLoS Neglected Tropical Diseases 01/2011; 5(1):e934. · 4.57 Impact Factor
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    ABSTRACT: Kawasaki disease (KD) is characterized by systemic vasculitis with unknown etiology. Previous studies from Japan indicated that a gene polymorphism of ITPKC (rs28493229) is responsible for susceptibility to KD. We collected DNA samples from 1,531 Taiwanese subjects (341 KD patients and 1,190 controls) for genotyping ITPKC. In this study, no significant association was noted for the ITPKC polymorphism (rs28493229) between the controls and KD patients, although the CC genotype was overrepresented. We further combined our data with previously published case/control KD studies in the Taiwanese population and performed a meta-analysis. A significant association between rs28493229 and KD was found (Odds Ratio:1.36, 95% Confidence Interval 1.12-1.66). Importantly, a significant association was obtained between rs28493229 and KD patients with aneurysm formation (P = 0.001, under the recessive model). Taken together, our results indicated that C-allele of ITPKC SNP rs28493229 is associated with the susceptibility and aneurysm formation in KD patients in a Taiwanese population.
    PLoS ONE 01/2011; 6(4):e17370. · 3.53 Impact Factor
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    ABSTRACT: Kawasaki 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 (P=0.0535 under the dominant model; P=0.0575 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 (P=0.009, 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.
    Journal of Human Genetics 12/2010; 56(2):161-5. · 2.53 Impact Factor
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    ABSTRACT: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology and primarily affects children less than 5 years of age. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) has been suggested as a candidate gene for conferring susceptibility to autoimmunity. This study examined the correlation of CTLA-4 gene polymorphisms in KD with and without coronary artery lesions (CAL). A total of 233 KD patients and 644 controls were subjected to determination of CTLA-4 polymorphisms at (-318) C/T and (+49) A/G positions by restriction fragment length polymorphism. Susceptibility, CAL, and intravenous immunoglobulin treatment response of KD were then analyzed with genetic variants. Polymorphisms of CTLA-4 (+49 A/G) and (-318 C/T) were not significantly different between normal children and patients with KD. The CTLA-4 (+49) A allele (AA+AG genotype), however, was significantly associated with CAL formation, especially in female patients. This study provides the first evidence supporting the association of CTLA-4 (+49) A/G polymorphism with the CAL formation of KD particularly in female patients.
    Journal of Clinical Immunology 11/2010; 31(2):240-4. · 3.38 Impact Factor

Publication Stats

93 Citations
20.07 Total Impact Points

Institutions

  • 2010–2014
    • Chang Gung Memorial Hospital
      • Division of Rheumatology, Allergy and Immunology
      T’ai-pei, Taipei, Taiwan