Interferon-gamma Genetic Polymorphism and Expression in Kawasaki Disease

Huang, Ying‐Hsien; Hsu, Yi‐Hsiang; Lu, Hsing‐Fang; Wong, Henry Sung-Ching; Yu, Hong‐Ren; Kuo, Hsing‐Chun; Huang, Fay; Chang, Wei‐Chiao; Kuo, Ho-Chang

doi:10.1097/md.0000000000003501

Cited by 35 publications

(28 citation statements)

References 41 publications

(61 reference statements)

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“…Furthermore, we have demonstrated that hepcidin levels are elevated in KD patients [14,15]. Following IVIG administration, KD patients' plasma hepcidin levels significantly decreased, and their changes were related to IVIG treatment resistance and CAL formation development [8,14]. We further reported that the upregulation of hepcidin induces transient hypoferremia, while anemia has also been associated with disease outcomes in acute-phase KD [7,16].…”

Section: Introductionmentioning

confidence: 77%

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HAMP promoter hypomethylation and increased hepcidin levels as biomarkers for Kawasaki disease

Huang

Kuo

et al. 2018

Journal of Molecular and Cellular Cardiology

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Kawasaki disease (KD) is the most common coronary vasculitis to appear in children with anemia and has been associated with elevated plasma hepcidin levels. We recruited a total of 241 cases, including 18 KD patients, who were tested both prior to receiving intravenous immunoglobulin (IVIG) and at least 3 weeks after IVIG treatment, and 18 febrile controls, who were observed in the Illumina HumanMethylation450 BeadChip study for their CpG markers. The remaining cases consisted of another 92 KD patients and 113 controls that were used for validation by pyrosequencing. We performed a genetic functional study using Luciferase assays. A support vector machine (SVM) classification model was adopted to identify KD patients and control subjects. In this study, KD patients clearly demonstrated a significantly epigenetic hypomethylation of HAMP promoter compared to controls. After receiving IVIG treatment, the hypomethylation status in KD patients was restored, and we observed a significant opposite tendency between the DNA methylation of target CpG sites (cg23677000 and cg04085447) and the hepcidin level. Furthermore, reporter gene assays were used to detect target CpG sites, the methylation of which displayed decreased levels of HAMP gene expression. Of particular note, we developed a SVM classification model with a 90.9% sensitivity, a 91.9% specificity, and 0.94 auROC in the training set. An independent blind cohort also had good performance (96.1% sensitivity and 89.7% specificity). In this study, we demonstrate HAMP promoter hypomethylation, which upregulates hepcidin expression in KD patients. Furthermore, the reliability and robustness of our SVM classification model can accurately serve as KD biomarkers.

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Section: Introductionmentioning

confidence: 77%

“…In addition to the five diagnostic criteria of KD, KD patients may also experience such clinical manifestations as hepatitis, pyuria, hypoalbuminemia, and anemia [5][6][7][8]. Of those, anemia is the most common clinical manifestation in KD patients [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

HAMP promoter hypomethylation and increased hepcidin levels as biomarkers for Kawasaki disease

Huang

Kuo

et al. 2018

Journal of Molecular and Cellular Cardiology

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“…We carried out genotyping using a TaqMan Allelic Discrimination Assay (Applied Biosystems, Foster City, CA, USA). PCR was performed quickly with a 96-well microplate in an ABI 9700 Thermal Cycler using the following thermal cycling conditions: denaturation at 95°C for 10 minutes, followed by 40 cycles of denaturation at 92°C for 15 seconds each, and then annealing and extension at 60°C for 1 min as previously described [ 42 ]. We used System SDS software version 1.2.3 to quantify and analyze fluorescence.…”

Section: Methodsmentioning

confidence: 99%

Correlation ofHAMPgene polymorphisms and expression with the susceptibility and length of hospital stays in Taiwanese children with Kawasaki disease

et al. 2017

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Kawasaki disease (KD) is a form of systemic vasculitis. Regarding its pathogenesis, HAMP gene encoding hepcidin, which is significant for iron metabolism, has a vital function. In this study, we recruited a total of 381 KD patients for genotyping. Data from 997 subjects (500 subjects from cohort 1; 497 subjects from cohort 2) were used for analysis. Using TaqMan allelic discrimination, we determined five tag SNPs (rs916145, rs10421768, rs3817623, rs7251432, and rs2293689). Treatment outcome data related to such clinical phenotypes as coronary artery lesions (CAL), coronary artery aneurysms (CAA), and intravenous immunoglobulin (IVIG) effects were also collected. Furthermore, we measured plasma hepcidin levels with an enzyme-linked immunosorbent assay. We found that HAMP gene polymorphism (rs7251432, and rs2293689) was significantly correlated with KD risk and that plasma hepcidin levels both before and after IVIG treatment had a significantly positive correlation with length of hospital stays (R = 0.217, p = 0.046 and R = 0.381, p < 0.0001, respectively). In contrast, plasma hepcidin levels has a negative correlation with KD patients’ albumin levels (R = −0.27, p < 0.001) prior to IVIG treatment. This study's findings indicate that HAMP might have a role in the disease susceptibility, as well as its expressions correlated length of hospital stays, and albumin levels in Taiwanese children with KD.

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“…Interferon‐ γ (Interferon‐gamma, IFN‐γ or IFNG ) is an important cytokine, which is mainly secreted by natural killer cells and CD80 + T cells 11 . The human IFN‐γ gene is located on chromosome 12 (12q14), containing 4 exons and 3 introns with approximately 6 kb 12 .…”

Section: Introductionmentioning

confidence: 99%

Association of IFN‐γ polymorphisms with ankylosing spondylitis risk

Liu

Zhang

Guan

et al. 2020

J Cellular Molecular Medi

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The case‐control study was designed to investigate the genetic effects of interferon‐gamma (IFN‐γ) rs2069727 and rs1861494 polymorphisms on ankylosing spondylitis (AS) susceptibility in a Chinese Han population. Blood samples were collected from 108 AS patients and 110 healthy controls. IFN‐γ polymorphisms were genotyped by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Hardy‐Weinberg equilibrium (HWE) test was performed in control group. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using chi‐square test to evaluate the association between AS susceptibility and IFN‐γ polymorphisms, and the results were adjusted by logistic regressive analysis. The frequency of rs2069727 CC genotype was much higher in cases than that in controls, suggested its significant association with increased AS risk (adjusted OR = 5.899, 95% CI = 1.563‐22.261; P = .009). In addition, C allele also showed close association with increased risk of AS (adjusted OR = 2.052, 95% CI = 1.286‐1.704, P = 0 .003). While the genotype and allele frequencies of IFN‐γ rs1861494 polymorphism were not significantly different between patients and controls (P > 0.05 for all), IFN‐γ rs2069727 polymorphism is significantly associated with increased AS risk in a Chinese Han Population.

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Interferon-gamma Genetic Polymorphism and Expression in Kawasaki Disease

Cited by 35 publications

References 41 publications

HAMP promoter hypomethylation and increased hepcidin levels as biomarkers for Kawasaki disease

HAMP promoter hypomethylation and increased hepcidin levels as biomarkers for Kawasaki disease

Correlation ofHAMPgene polymorphisms and expression with the susceptibility and length of hospital stays in Taiwanese children with Kawasaki disease

Association of IFN‐γ polymorphisms with ankylosing spondylitis risk

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