与川崎病冠状动脉病变形成相关的CYP2E1基因多态性
CYP2E1 Gene Polymorphisms Related to the Formation of Coronary Artery Lesions in Kawasaki Disease.
作者信息
Chang Ling-Sai, Hsu Yu-Wen, Lu Chien-Chang, Lo Mao-Hung, Hsieh Kai-Sheng, Li Sung-Chou, Chang Wei-Chiao, Kuo Ho-Chang
机构信息
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.
出版信息
Pediatr Infect Dis J. 2017 Nov;36(11):1039-1043. doi: 10.1097/INF.0000000000001657.
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.
背景
川崎病（KD）是一种扰乱冠状动脉的急性发热性全身性血管炎。研究发现，人类细胞色素P450基因多态性会显著增加患者发生不良心血管事件和亚临床动脉粥样硬化的风险。本研究旨在探讨细胞色素P450 2E1（CYP2E1）基因多态性与KD之间可能存在的关系。
方法
我们选择了CYP2E1基因的6个标签单核苷酸多态性（SNP），对340例KD患者进行TaqMan等位基因鉴别分析，并对临床表型和冠状动脉病变（CAL）进行分析。在逻辑回归中，对标签SNP与CAL的关联进行年龄和性别的校正。
结果
rs915906的CC基因型KD患者中CAL形成的比例更高（P = 0.009）。此外，rs2070676的GG基因型频率显示KD患者发生CAL形成的风险显著更高（P = 0.007）。然而，无论是否使用高剂量阿司匹林，CYP2E1基因的SNP均不影响参与研究的KD患者的CAL形成。通过表达数量性状位点分析，我们发现与KD患者CAL形成相关的SNP也会影响某些细胞类型中CYP2E1的表达。
结论
本研究首次发现KD患者CAL形成的风险与CYP2E1基因多态性有关。
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