CD40Gene Polymorphisms Associated with Susceptibility and Coronary Artery Lesions of Kawasaki Disease in the Taiwanese Population

Background. Kawasaki disease (KD) is characterized by systemic vasculitis of unknown etiology. Our previous studies showed expression ofCD40ligand on CD4+ T cells correlated to the coronary artery lesion (CAL) and disease progress in KD. Other studies from Japan suggested the role ofCD40Lin the pathogenesis of CAL, and this might help explain the excessive number of males affected with KD but cannot be reproduced by Taiwanese population. This study was conducted to investigate theCD40polymorphism in KD and CAL formation.Methods. A total of 950 subjects (381 KD patients and 569 controls) were investigated to identify 2 tagging single-nucleotide polymorphisms (tSNPs) ofCD40(rs4810485 and rs1535045) by using the TaqMan allelic discrimination assay.Results. A significant association was noted with regards toCD40tSNPs (rs1535045) between controls and KD patients (P=0.0405, dominant model). In KD patients, polymorphisms ofCD40(rs4810485) showed significant association with CAL formation (P=0.0436, recessive model). Haplotype analysis did not yield more significant results between polymorphisms ofCD40and susceptibility/disease activity of KD.Conclusions. This study showed for the first time that polymorphisms ofCD40are associated with susceptibility to KD and CAL formation, in the Taiwanese population.

Download Full-text

Association Between the lncRNA TDRG1 rs8506 C>T Polymorphism and Susceptibility To Kawasaki Disease in Chinese Children

10.21203/rs.3.rs-632870/v1 ◽

2021 ◽

Author(s):

Jinqing Li ◽

Kai Guo ◽

Hongyan Yu ◽

Yufen Xu ◽

Chuanzi Yang ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Systemic Vasculitis ◽

Recessive Model ◽

Chinese Children ◽

Future Research ◽

Human Testis ◽

Non Coding Rna ◽

Vegf Pathway ◽

Endothelial Growth Factor

Abstract Background Kawasaki disease (KD) is an acute systemic vasculitis with unknown pathogen, and the formation of coronary artery lesions/aneurysm (CAL/CAA) is the most common sequela. Environmental and genetic factors have been suggested to be involved in the pathogenesis of KD. Human testis development related 1(TDRG1) is a newly identified long non-coding RNA (lncRNA) which stimulates the vascular endothelial growth factor (VEGF) pathway. The aim of this study was to investigate the association between genetic polymorphism of TDRG1 and the risk of KD. Methods A total of two cohorts from Guangzhou (988 KD patients and 1054 controls) and Beijing (564 KD patients and 1221 controls) were enrolled in the present study. Rs8506 of TDRG1 was chosen for TaqMan genotyping assay. Results Logistic regression suggested that lncRNA TDRG1 rs8506 C > T polymorphism was not associated with the risk of KD in both Guangzhou and Beijing cohort (dominant model and recessive model: P > 0.05). Moreover, we also did not observe a significant association between the lncRNA TDRG1 rs8506 C > T polymorphism and the risk of KD patients with different ages, gender or coronary artery outcomes in both Guangzhou and Beijing cohort. Conclusions The present study revealed that the lncRNA TDRG1 rs8506 C > T polymorphism might not be associated with susceptibility to KD in Chinese children. Future research with a larger sample size should be performed to confirm these results.

Download Full-text

Epidemiological Features and Clinical Study of Kawasaki Disease in Iran

ACTA MEDICA IRANICA ◽

10.18502/acta.v58i12.5154 ◽

2021 ◽

Author(s):

Parvin Akbariasbagh ◽

Saharnaz Talebiyan ◽

Yahya Aghighi ◽

Reza Raeeskarai ◽

Amirhosein Seyedhoseinpour ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Clinical Features ◽

Systemic Vasculitis ◽

Febrile Illness ◽

Developed Countries ◽

Response To Treatment ◽

Unknown Etiology ◽

Laboratory Findings ◽

Female Ratio

Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology and the major cause of pediatric acquired cardiac disease worldwide, particularly in developed countries. This study characterizes the epidemiologic and clinical features of KD in the Pediatric Rheumatology Department service in a general hospital. 120 patients with the diagnosis of KD between 1990 and 2009 were enrolled. We investigated the epidemiologic and clinical features of coronary artery involvement of the patients. Frequency of many parameters including age, sex, season, clinical and laboratory findings, response to treatment, and complications of the patients determined. During the 20-year study period, 120 patients <15 years of age were admitted for KD. Among them, 39.2% were at the extremes of the age spectrum, with 2.5% <6 months and 36.7% >5 years of age, male to female ratio of 1.3:1 and the classic KD to incomplete KD ratio of 3.1:1. KD recurred in 5% of all cases. It occurred most frequently in the winter and least frequently in the summer. The occurrence of coronary artery abnormalities (CAA) was 4.2%. Kawasaki disease should be considered in any pediatric patients with a prolonged refractory febrile illness in order to prevent CAA formation.

Download Full-text

A Retrospective Cohort Study of Kawasaki Disease in Hue Central Hospital for 10 Years (2010–2019)

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.3858 ◽

2020 ◽

Vol 8 (B) ◽

pp. 99-103

Author(s):

Nguyen Huu Son ◽

Tran Kiem Hao ◽

Nguyen Thi Hoang Anh

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Gamma Globulin ◽

Systemic Vasculitis ◽

Cervical Lymphadenopathy ◽

Response To Therapy ◽

High Rate ◽

Unknown Etiology ◽

Central Hospital ◽

Laboratory Findings

INTRODUCTION: Kawasaki disease (KD) is an acute self-limited systemic vasculitis of unknown etiology which affects mainly children <5 years of age. If the disease is left untreated, it can lead to serious complications such as inflammation of the blood vessels. AIM: We aim to evaluate the clinical and laboratory findings and response to therapy of KD at Hue Central Hospital. METHODS: This is a retrospective study of patients with KD at Pediatric Center of Hue Central Hospital between January 2010 and December 2019. Clinical and laboratory examinations as well as the echocardiograms finding were analyzed. RESULTS: All patients were under 5 years old, in which boys were more than girls. Fever lasting over 5 days, changing in the mouth mucosa, and peripheral extremities were seen in all patients. About 73.2% had bilateral conjunctivitis and 78.0% had rash. About 42.3% of patients had cervical lymphadenopathy. Laboratory findings were noted with 84.5% of patients had hyperleukocytosis (>12,000/ mm3), 76.2% of patients had high serum C-reactive protein (CRP) levels (>100 mg/dl), 56% of patients had erythrocyte sediment rate >60 mm in the 1st h, and 34.5% of patients had thrombocytosis (platelet count >500,000/mm3) at the time of diagnosis. About 26.2% of patients had coronary artery lesions. Most patients (84.4%) had good outcome since the first dose of gamma-globulin and 13% of patients needed the second dose. There was a significant correlation between coronary artery abnormalities and no or late treatment of gamma-globulin. CONCLUSION: KD was very common in children under 5 years old with the high rate of coronary artery lesion. Treatment with gamma-globulin on or before 10 days of fever resulted in better coronary outcomes and decreased the total length of time of clinical symptoms.

Download Full-text

The Relationship Between TNF-Like Protein 1A and Coronary Artery Aneurysms in Children With Kawasaki Disease

10.21203/rs.3.rs-274389/v1 ◽

2021 ◽

Author(s):

jing zhang ◽

Haobo Weng ◽

Qiongfei Pei ◽

Penghui Yang ◽

Wentao Fan ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Development Process ◽

Systemic Vasculitis ◽

Artery Aneurysm ◽

Unknown Etiology ◽

Coronary Artery Aneurysms ◽

Tnf Superfamily ◽

The Relationship ◽

Necrosis Factor

Abstract Background: Kawasaki disease (KD) is an acute, systemic vasculitis of unknown etiology that occurs predominantly in infants and children, and the most crucial complication of KD is coronary artery aneurysm (CAA). Tumor necrosis factor (TNF)-like protein 1A (TL1A) is a member of the TNF superfamily, which possesses the ability of maintaining vascular homeostasis and regulating immune response. This study aims to examine the serum TL1A levels in KD patients, and to investigate the relationship between TL1A and CAAs in children with KD.Methods: Blood samples were recruited from 119 KD patients, 35 febrile controls (FCs) and 37 healthy controls (HCs). The KD group was further divided into KD with CAAs (KD-CAAs) and KD non-CAAs (KD-NCAAs) groups. Serum TL1A levels were measured using enzyme-linked immunosorbent assays, and clinical parameters were collected in KD patients. Results: Serum TL1A levels in the acute phase of KD patients were significantly higher than that in the FC and HC groups. In particular, serum TL1A were substantially increased in the KD-CAA group than that in the KD-NCAA group. Furthermore, TL1A levels were positively correlated with the duration of fever, time point of IVIG and WBC levels, but negatively correlated with levels of RBC, Hb and Albumin in the KD group. Conclusions: TL1A might be involved in the KD-associated vasculitis, and might be a factor in the development process of CAAs.

Download Full-text

The miRNA-608 rs4919510 G>C polymorphism confers reduce coronary injury of Kawasaki disease in a Southern Chinese population

Bioscience Reports ◽

10.1042/bsr20181660 ◽

2019 ◽

Vol 39 (5) ◽

Author(s):

Yanfei Wang ◽

Zhaoliang Lu ◽

Lanyan Fu ◽

Yaqian Tan ◽

Di Che ◽

...

Keyword(s):

Kawasaki Disease ◽

Systemic Vasculitis ◽

Mucocutaneous Lymph Node Syndrome ◽

Allelic Discrimination Assay ◽

Allelic Discrimination ◽

Taqman Allelic Discrimination ◽

Southern Chinese ◽

Immune Mediated ◽

Single Locus Analysis ◽

The Relationship

Abstract Kawasaki disease (KD) is also called mucocutaneous lymph node syndrome and is an acute febrile pediatric disease characterized by systemic vasculitis. KD typically occurs in children 5 years old or younger and occurs more often in males than in females. miRNA-608 has been reported to interact with interleukin-6 and affect innate immunity. The immune-mediated inflammation could induce the occurrence of KD; however, there is no previous research focused on the relationship between miRNA-608 polymorphism and the KD risk. The present study explored the correlation between the miRNA-608 rs4919510 G>C polymorphism and the risk for KD. We recruited 532 patients with KD and 623 controls to genotype the miRNA-608 rs4919510 G>C polymorphism with a TaqMan allelic discrimination assay. Single-locus analysis showed no significant association between miRNA rs4919510 G>C polymorphism and KD susceptibility. However in an analysis stratified by age, gender, and coronary artery lesion (CAL), we found a relationship between the miRNA-608 rs4919510 G>C polymorphism and KD susceptibility. When KD patients were stratified by coronary injury, the CG/CC genotypes of the miRNA-608 rs4919510 G>C polymorphism contributed to a higher occurrence of KD than that was found in the GG genotype patients (adjusted odds ratio = 0.74, 95% CI = 0.56–0.98, P = 0.033). The present study demonstrated that the miRNA-608 rs4919510 G>C polymorphism may have a CAL-related relationship with KD susceptibility that has not been previously revealed.

Download Full-text

The Association between Single-Nucleotide Polymorphisms ofORAI1Gene and Breast Cancer in a Taiwanese Population

The Scientific World JOURNAL ◽

10.1100/2012/916587 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Wei-Chiao Chang ◽

Peng Yeong Woon ◽

Yu-Wen Hsu ◽

Shengyu Yang ◽

Yi-Ching Chiu ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptors ◽

Cancer Patients ◽

Cancer Progression ◽

Nucleotide Polymorphisms ◽

Breast Cancer Patients ◽

Nodal Involvement ◽

Taiwanese Population ◽

Allelic Discrimination Assay ◽

Allelic Discrimination

Background. Breast cancer is the most common malignancy in women. There is increasing evidence suggesting thatORAI1, components of store-operated calcium channel, play a pivotal role in breast cancer progression and metastasis.Methods. A total of 384 female patients with breast cancer were included in this study. We selected five representative taggingORAI1SNPs from HapMap database with minimum allele frequency (MAF)>10%. Genotyping was performed using TaqMan allelic discrimination assay. Chi-square (χ2) test was used to analyze statistical differences among control and patient groups in genotype and allelic frequencies.Results. Two of theORAI1SNPs (rs12320939 and rs12313273) were associated with estrogen receptors positive in breast cancer patients under the recessive model. When the Bonferroni correction was performed, the significance still existed. In addition, rs12320939 also associated with the lymph nodal involvement.Conclusion. We showed that genetic polymorphisms ofORAI1associated strongly with lymph nodal involvement and estrogen receptors (ERs) positive breast cancer patients in a Taiwanese population.

Download Full-text

Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.130138 ◽

2010 ◽

Vol 70 (3) ◽

pp. 454-462 ◽

Cited By ~ 59

Author(s):

LM Diaz-Gallo ◽

P Gourh ◽

J Broen ◽

C Simeon ◽

V Fonollosa ◽

...

Keyword(s):

Systemic Sclerosis ◽

Meta Analysis ◽

The Novel ◽

Nucleotide Polymorphisms ◽

Allelic Discrimination Assay ◽

Allelic Discrimination ◽

Single Nucleotide ◽

Independent Replication ◽

First Time

ObjectiveTwo functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes.Methods3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc.ResultsThe meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (pFDRcorrected=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (pFDRcorrected=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (pFDRcorrected=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1).ConclusionThe study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.

Download Full-text

Pulse Wave Velocity in Kawasaki Disease

Angiology ◽

10.1177/0003319716651789 ◽

2016 ◽

Vol 68 (3) ◽

pp. 189-195 ◽

Cited By ~ 2

Author(s):

Yoshitaka Iwazu ◽

Takaomi Minami ◽

Kazuhiko Kotani

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Arterial Stiffness ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Pulse Wave ◽

Systemic Vasculitis ◽

Unknown Etiology ◽

Limited Information ◽

Coronary Artery Aneurysms

Kawasaki disease (KD) is an acute childhood febrile disease of unknown etiology. It exhibits not only coronary artery aneurysms in some cases but also systemic vasculitis. Whether KD is associated with accelerated atherosclerosis remains debatable. The measurement of pulse wave velocity (PWV) is useful as a simple, noninvasive measurement of arterial stiffness, an atherosclerotic manifestation. We herein present a systematic review of clinical studies that focused on PWV in patients with KD. A PubMed-based search identified 8 eligible studies published until June 2015. The PWV of patients with KD, regardless of antecedent coronary artery lesions, was high relative to controls, even though their blood pressure appeared to be similar. Although definitive conclusions cannot be made with the limited information, patients with KD may be at risk of systemic atherosclerosis in association with arterial stiffness. Further research, including longitudinal and outcome studies, is needed to determine the clinical significance of a potential increase in PWV in patients with KD.

Download Full-text

HMGB1 gene polymorphism is associated with coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease

Rheumatology ◽

10.1093/rheumatology/key356 ◽

2018 ◽

Vol 58 (5) ◽

pp. 770-775 ◽

Cited By ~ 6

Author(s):

Jong Gyun Ahn ◽

Yoonsun Bae ◽

Dongjik Shin ◽

Jiho Nam ◽

Kyu Yeun Kim ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Single Nucleotide Polymorphisms ◽

Odds Ratio ◽

Ivig Treatment ◽

Nucleotide Polymorphisms ◽

Coronary Artery Lesions ◽

Hmgb1 Level ◽

Single Nucleotide ◽

Ivig Resistance

Abstract Objectives Kawasaki disease (KD) is an acute systemic vasculitis of unknown aetiology that affects infants and young children. Recent reports of elevated serum high mobility group box 1 (HMGB1) level during the acute phase of KD and its relationship to poor response to IVIG treatment suggest a possible association of HMGB1 polymorphisms with KD. We investigated the association between the polymorphisms of the HMGB1 gene, KD susceptibility, coronary artery lesions, and KD response to IVIG treatment. Methods Whole genome sequencing of the HMGB1 gene was performed to identify causative variants. Two tagging single nucleotide polymorphisms of the HMGB1 gene were selected using linkage disequilibrium analysis. The tagging single nucleotide polymorphisms were genotyped using the TaqMan Allelic Discrimination assay in a total of 468 subjects (265 KD patients and 203 controls). Results The HMGB1 single nucleotide polymorphisms were not associated with KD susceptibility. However, in KD patients, there was a significant association of rs1412125 with coronary artery lesions formation in the recessive model (GG vs AA + GA: odds ratio = 4.98, 95% CI = 1.69–14.66, P = 0.005). In addition, rs1412125 was associated with IVIG resistance in the recessive (GG vs AA + GA: odds ratio = 4.11, 95% CI = 1.38–12.23, P = 0.017) and allelic models (G vs A: odds ratio = 1.80, 95% CI = 1.06–3.06, P = 0.027). Conclusion The rs1412125 in HMGB1 might be a risk factor for the development of coronary artery lesions and IVIG resistance in KD patients.

Download Full-text

Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase 1 Influenced the Age Onset of Parkinson’s Disease

10.20944/preprints202009.0470.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Nóra Török ◽

Rita Maszlag-Török ◽

Kinga Molnár ◽

Zoltán Szolnoki ◽

Ferenc Somogyvári ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Subgroup Analysis ◽

Snp Analysis ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Allelic Discrimination Assay ◽

Allelic Discrimination ◽

Single Nucleotide ◽

Indoleamine 2,3 Dioxygenase ◽

Tryptophan Dioxygenase

Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

Download Full-text