Ling-Sai Chang1, Yu-Wen Hsu, Chien-Chang Lu, Mao-Hung Lo, Kai-Sheng Hsieh, Sung-Chou Li, Wei-Chiao Chang, Ho-Chang Kuo. 1. From the *Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, and †Chang Gung University College of Medicine, and ‡Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; §The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, and ¶Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; ‖Division of Colorectal Surgery, Department of Surgery, and **Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; ††Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; ‡‡Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan; §§Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan.
Abstract
BACKGROUND: Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients' risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between cytochrome P450, family 2, subfamily E and polypeptide 1 (CYP2E1) polymorphisms with KD. METHODS: We selected 6 tag single-nucleotide polymorphisms (SNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KD patients and performed analysis on the clinical phenotypes and coronary artery lesions (CALs). CAL associations of tag SNPs were adjusted for age and gender in the logistic regression. RESULTS: The KD patients with a CC genotype of rs915906 demonstrated a greater proportion of CAL formation (P = 0.009). Furthermore, the GG genotype frequencies of rs2070676 showed a significantly greater risk for CAL formation in KD patients (P = 0.007). However, the SNPs of the CYP2E1 gene did not influence CAL formation in the participating KD patients either with or without high-dose acetylsalicylic acid. Using the expression quantitative trait locus analyses, we found that the SNPs associated with CAL formation in KD also affected CYP2E1 expression in certain cell types. CONCLUSION: This study is the first to find that the risk of CAL formation is related to CYP2E1 gene polymorphisms in KD patients.
BACKGROUND:Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients' risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between cytochrome P450, family 2, subfamily E and polypeptide 1 (CYP2E1) polymorphisms with KD. METHODS: We selected 6 tag single-nucleotide polymorphisms (SNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KDpatients and performed analysis on the clinical phenotypes and coronary artery lesions (CALs). CAL associations of tag SNPs were adjusted for age and gender in the logistic regression. RESULTS: The KDpatients with a CC genotype of rs915906 demonstrated a greater proportion of CAL formation (P = 0.009). Furthermore, the GG genotype frequencies of rs2070676 showed a significantly greater risk for CAL formation in KDpatients (P = 0.007). However, the SNPs of the CYP2E1 gene did not influence CAL formation in the participating KDpatients either with or without high-dose acetylsalicylic acid. Using the expression quantitative trait locus analyses, we found that the SNPs associated with CAL formation in KD also affected CYP2E1 expression in certain cell types. CONCLUSION: This study is the first to find that the risk of CAL formation is related to CYP2E1 gene polymorphisms in KDpatients.
Authors: Ling-Sai Chang; Jia-Huei Yan; Jin-Yu Li; Deniz Des Yeter; Ying-Hsien Huang; Mindy Ming-Huey Guo; Mao-Hung Lo; Ho-Chang Kuo Journal: Int J Environ Res Public Health Date: 2020-05-25 Impact factor: 3.390