Association of MnSOD gene polymorphism with susceptibility to Kawasaki disease in Chinese children

Abstract Background: Kawasaki disease is a type of acute febrile rash disease that is common in children and is characterised by primary lesions of systemic middle and small vasculitis, which can lead to coronary artery lesions. Manganese superoxide dismutase (MnSOD), one of the most important antioxidases in the human body, plays a key role in maintaining the balance of free radicals in the human body. Two single-nucleotide polymorphisms (SNPS) (rs4880 and rs5746136) in the MnSOD gene were related to oxidative stress disease. The purpose of this study is to explore the possible relationship between MnSOD gene polymorphisms and Kawasaki disease susceptibility. Methods: This study included 100 Kawasaki disease children and 102 healthy children. Two single-nucleotide polymorphisms (rs4880 and rs5746136) were detected by polymerase chain reaction sequence-based typing. Results: There was a significant difference in both the genotype frequency (χ2 = 10.805, p = 0.005) and the allele frequency (χ2 = 7.948, p = 0.005) of rs5746136 between the Kawasaki disease group and the control group. Children with the A allele had a 0.558 times lower risk of Kawasaki disease than those without the A allele (χ2 = 7.948, p = 0.005, odds ratio = 0.558, 95% confidence interval = 0.371–0.838). There was no significant difference in the genotype and gene frequencies of rs5746136 between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesion groups (p > 0.05), and there was no significant difference in the rs4880 genotype and allele frequencies between the Kawasaki disease and healthy control groups or between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesions groups (p > 0.05). Conclusion: This study provides evidence supporting an association between MnSOD gene polymorphisms and susceptibility to Kawasaki disease. The genotype AA and the allele A of the MnSOD gene locus rs5746136 were risk factors for Kawasaki disease.

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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.

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The IL-1B Gene Polymorphisms rs16944 and rs1143627 Contribute to an Increased Risk of Coronary Artery Lesions in Southern Chinese Children with Kawasaki Disease

Journal of Immunology Research ◽

10.1155/2019/4730507 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Lan Yan Fu ◽

Xiantao Qiu ◽

Qiu Lian Deng ◽

Ping Huang ◽

Lei Pi ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Gene Polymorphisms ◽

Chinese Population ◽

Healthy Children ◽

Nucleotide Polymorphisms ◽

Coronary Artery Lesions ◽

Multicenter Studies ◽

Southern Chinese ◽

Increased Risk

Background. Kawasaki disease (KD) is a systemic form of self-limited vasculitis in children less than five years old, and the main complication is coronary artery injury. However, the etiology of KD remains unclear. The IL-1B polymorphisms rs16944 GG and rs1143627 AA and their diplotype GA/GA have been associated with significantly increased risk of intravenous immunoglobulin (IVIG) resistance in a Taiwanese population, but the relationship between rs16944 A/G and rs1143627 G/A and coronary artery lesions (CALs) in patients with KD has not been investigated. The present study is aimed at investigating whether the rs16944 A/G and rs1143627 G/A polymorphisms in IL-1B were associated with KD susceptibility and CALs in a southern Chinese population. Methods and Results. We recruited 719 patients with KD and 1401 healthy children. Multiplex PCR was used to assess the genotypes of single nucleotide polymorphisms (SNPs), including two SNPs of IL-1B, rs16944 A/G and rs1143627 G/A. According to the results, no significant association was observed between the IL-1B (rs16944 and rs1143627) polymorphisms and KD risk in the patients compared with the healthy controls in our southern Chinese population. However, in further stratified analysis, we found that children younger than 12 months with the rs16944 GG and rs1143627 AA genotypes of IL-1B had a higher risk of CALs than those with the AA/AG genotypes of rs16944 and GG/AG genotypes of rs1143627 (OR=2.28, 95% CI=1.32-3.95, P=0.0032, adjusted OR=2.33, 95% CI=1.34-4.04, P=0.0027). Conclusions. Our results indicated that there was no association between the rs16944 A/G and rs1143627 G/A gene polymorphisms and KD susceptibility. However, the rs16944 GG and rs1143627 AA genotypes of IL-1B may significantly impact the risk of CAL formation in children younger than 12 months, which may contribute to the pathogenesis of KD. These findings need further validation in multicenter studies with larger sample sizes.

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Lack of Association betweenCLEC5AGene Single-Nucleotide Polymorphisms and Kawasaki Disease in Taiwanese Children

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/398628 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Ya-Ling Yang ◽

Wei-Pin Chang ◽

Yu-Wen Hsu ◽

Wei-Chiao Chen ◽

Hong-Ren Yu ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Single Nucleotide Polymorphisms ◽

Treatment Response ◽

Intravenous Immunoglobulin ◽

Coronary Artery Lesion ◽

Nucleotide Polymorphisms ◽

Lesion Formation ◽

Single Nucleotide ◽

Immunoglobulin Treatment

Background. Kawasaki disease is characterized by systemic vasculitis of unknown etiology. Previous genetic studies have identified certain candidate genes associated with susceptibility to KD and coronary artery lesions. Host innate immune response factors are involved in modulating the disease outcome. The aim of this study was to investigate CLEC5A (C-type lectin domain family 5) genetic polymorphisms with regards to the susceptibility and outcome of KD.Methods. A total of 1045 subjects (381 KD patients and 664 controls) were enrolled to identify 4 tagging single-nucleotide polymorphisms (tSNPs) ofCLEC5A(rs1285968, rs11770855, rs1285935, rs1285933) by using the TaqMan Allelic Discrimination Assay. The Hardy-Weinberg equilibrium was assessed in cases and controls, and genetic effects were evaluated by the chi-square test.Results. No significant associations were noted between the genotypes and allele frequency of the 4CLEC5AtSNPs between controls and patients. In the patients, polymorphisms ofCLEC5Ashowed no significant association with coronary artery lesion formation and intravenous immunoglobulin treatment response.Conclusions. This study showed for the first time that polymorphisms ofCLEC5Aare not associated with susceptibility to KD, coronary artery lesion formation, and intravenous immunoglobulin treatment response in a Taiwanese population.

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Single-Nucleotide Polymorphism rs7251246 in ITPKC Is Associated with Susceptibility and Coronary Artery Lesions in Kawasaki Disease

PLoS ONE ◽

10.1371/journal.pone.0091118 ◽

2014 ◽

Vol 9 (3) ◽

pp. e91118 ◽

Cited By ~ 23

Author(s):

Ho-Chang Kuo ◽

Yu-Wen Hsu ◽

Mao-Hung Lo ◽

Ying-Hsien Huang ◽

Shu-Chen Chien ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Coronary Artery ◽

Kawasaki Disease ◽

Coronary Artery Lesions ◽

Nucleotide Polymorphism ◽

Single Nucleotide

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Association of PECAM-1 Gene Polymorphisms with Kawasaki Disease in Chinese Children

Disease Markers ◽

10.1155/2017/2960502 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Zhuoying Li ◽

Dong Han ◽

Jie Jiang ◽

Jia Chen ◽

Lang Tian ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Kawasaki Disease ◽

Gene Polymorphisms ◽

Cell Adhesion Molecule ◽

Systemic Vasculitis ◽

Healthy Children ◽

Coronary Artery Lesions ◽

Artery Disease ◽

The Relationship

Kawasaki disease (KD) is an acute systemic vasculitis complicated by development of coronary artery lesions. PECAM-1 is a kind of cell adhesion molecule, which plays an important role in coronary artery disease. The relationship between PECAM-1 gene polymorphisms and their susceptibility to Kawasaki diseases (KD) is still unclear. In our study, we examined the PECAM-1 gene polymorphisms in 44 KD patients and 59 healthy children and revealed the correlation of PECAM-1 gene polymorphisms in KD children with and without coronary artery lesions (CAL).

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CYP2E1 Gene Polymorphisms Related to the Formation of Coronary Artery Lesions in Kawasaki Disease

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0000000000001657 ◽

2017 ◽

Vol 36 (11) ◽

pp. 1039-1043 ◽

Cited By ~ 4

Author(s):

Ling-Sai Chang ◽

Yu-Wen Hsu ◽

Chien-Chang Lu ◽

Mao-Hung Lo ◽

Kai-Sheng Hsieh ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Gene Polymorphisms ◽

Coronary Artery Lesions ◽

Cyp2e1 Gene

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The Occurrence of Coronary Artery Lesions in Kawasaki Disease Based on C-reactive Protein Levels: A Retrospective Cohort Study

10.21203/rs.3.rs-113714/v1 ◽

2020 ◽

Author(s):

Hyo Soon An ◽

Gi-Beom Kim ◽

Mi Kyoung Song ◽

Sang Yun Lee ◽

Hye Won Kwon ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Demographic Data ◽

Artery Aneurysm ◽

Nationwide Survey ◽

Coronary Artery Lesions ◽

C Reactive Protein ◽

Reactive Protein ◽

Significant Difference ◽

Z Scores

Abstract BackgroundThis study aimed to assess the occurrence of coronary artery lesions (CAL) in patients with Kawasaki disease (KD) according to serum C-reactive protein (CRP) levels. MethodsThis retrospective analysis was based on the nationwide survey of KD conducted in the Republic of Korea between 2015 and 2017. We enrolled 9131 patients and defined low (<3 mg/dL) and high (≥3 mg/dL) CRP groups. Demographic data, clinical characteristics, z-scores, and scores based on the Japanese criteria for CAL were compared between the two groups. Logistic regression analysis was used to identify CAL risk factors.ResultsThe low CRP group accounted for 23% of patients. A significant difference was observed for the mean age at diagnosis (high vs. low CRP, 34.4 ± 24.9 vs. 31.7 ± 24.8 months, p<0.001) and fever duration (high vs. low CRP, 6.6 ± 2.2 vs. 6.3 ± 2.5 days, p<0.001). A non-response to intravenous immunoglobulin treatment was found in 1377 patients (20.1%) and 225 patients (11.7%) in the high and low CRP groups, respectively (p<0.001). CAL were found in 12.9% and 18.3% of the high and low CRP patients, respectively (p<0.001), based on z-scores; and in 9.9% and 12.5%, respectively (p = 0.001), based on the Japanese criteria in the acute phase. The giant coronary artery aneurysm occurrence ratio was similar between groups (p=1.0).ConclusionsCAL occurred in patients with both high and low CRP. Therefore, patients with KD should be carefully monitored regardless of their CRP levels.

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Influence of TLR-8 Gene Polymorphisms (rs3764880 and rs3788935) Associated to Pulmonary Tuberculosis in Kupang, Indonesia

Indonesian Journal of Tropical and Infectious Disease ◽

10.20473/ijtid.v9i1.22056 ◽

2021 ◽

Vol 9 (1) ◽

pp. 9

Author(s):

Afandi Charles ◽

Simeon Penggoam ◽

Ani Melani Maskoen ◽

Edhyana Sahiratmadja

Keyword(s):

Pulmonary Tuberculosis ◽

Intracellular Signaling ◽

Gene Polymorphisms ◽

Pathogenic Bacteria ◽

Nucleotide Polymorphisms ◽

Toll Like Receptor ◽

Single Nucleotide ◽

Significant Difference ◽

Hardy Weinberg Equilibrium ◽

Control Study

Toll-like receptor 8 (TLR-8) is known as part of intracellular signaling transduction for bacterial phagocytosis. Mycobacterium tuberculosis (Mtb) is intracellular pathogenic bacteria that is recognized by this receptor, and genetic variation of TLR-8 might alter susceptibility of the host towards pulmonary tuberculosis (PTB). This study aimed to determine whether TLR-8 gene polymorphisms were associated to PTB in Kupang, Indonesia. This case-control study compared demographic and clinical data between 115 PTB patients and 115 controls, then two TLR-8 single nucleotide polymorphisms (rs3764880 and rs3788935) were explored using the GoldenGate® Genotyping for VeraCode® / BeadXpress Illumina®. There is no significant difference between sex distribution of patient vs control groups. The polymorphisms (rs3764880 and rs3788935) are in Hardy-Weinberg Equilibrium in this population (p > 0.05). The distribution of major vs minor genotypes and alleles of TLR-8 polymorphisms in PTB patients were as followed: rs3764880 (GG vs GA vs AA, 50.0% vs 21.4% vs 28.6% ; G vs A, 60.9% vs 39.1% ) and rs3788935 (GG vs GA vs AA, 53.0% vs 21.7% vs 25.3%; G vs A, 62.9% vs 37.1%). Neither genotypes nor alleles were associated with PTB in this population (P > 0.05). Besides, when the analyses were stratified by gender, none of the alleles of polymorphism in both genders were associated with PTB cases. None of the TLR-8 polymorphisms have associated the risk of developing PTB in Kupang, East Nusa Tenggara population (as opposed to other studies in different ethnic groups). These might reflect the diversity of genetic polymorphisms in eastern Indonesia populations, suggesting different genetic backgrounds with western part of Indonesia.

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