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CYP2C19 失功能变异是导致早发性脑梗死的独立危险因素:一项基于医院的回顾性研究。

CYP2C19 loss-of-function variants are independent risk factors for premature cerebral infarction: a hospital based retrospective study.

机构信息

Department of Neurology, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, Meizhou, China.

Department of Prenatal Diagnostic Center, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, Meizhou, China.

出版信息

BMC Cardiovasc Disord. 2024 Oct 29;24(1):602. doi: 10.1186/s12872-024-04269-0.

Abstract

OBJECTIVE

Cytochrome P450 2C19 (CYP2C19) plays an vital role in the course of cardiovascular and cerebrovascular diseases by affecting lipid metabolism. Triglyceride-glucose (TyG) is a comprehensive index composed of triglyceride and blood glucose, has relationship with some diseases. There was no research report on the association CYP2C19 polymorphisms, TyG with premature cerebral infarction (CI) (onset ≤ 65 years old) susceptibility.

METHODS

This study retrospectively analyzed 1953 CI patients aged ≤ 65 years old from December 2018 to March 2024, and 1919 age-matched individuals with non-CI as controls. The relationship between CYP2C19 polymorphisms, TyG and premature CI risk were analyzed.

RESULTS

The proportion of hypertension, and diabetes mellitus in patients with premature CI was higher than those in controls. The serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and TyG levels in patients with premature CI were significantly higher than those in controls (all p < 0.05). The patients had lower CYP2C19 *1 allele frequency (63.3% vs. 69.6%, p < 0.001) and higher CYP2C19 *2 allele frequency (31.3% vs. 25.4%, p < 0.001) than controls. Logistic regression analysis showed that smoking history (odds ratio (OR): 1.193, 95% confidence interval (CI): 1.002-1.422, p = 0.048), hypertension (OR: 3.371, 95% CI: 2.914-3.898, p < 0.001), diabetes mellitus (OR: 1.911, 95% CI: 1.632-2.237, p < 0.001), CYP2C19 intermediate metabolizer (IM) + poor metabolizer (PM) phenotypes (OR: 1.424, 95% CI: 1.243-1.631, p < 0.001), and dyslipidemia (OR: 1.294, 95% CI: 1.077-1.554, p = 0.006) were independent risk factors for premature CI.

CONCLUSIONS

History of smoking, hypertension, diabetes mellitus, dyslipidemia, and CYP2C19 IM + PM phenotypes were independently associated with premature CI susceptibility.

摘要

目的

细胞色素 P450 2C19(CYP2C19)通过影响脂质代谢在心血管和脑血管疾病的发生发展中发挥重要作用。甘油三酯-葡萄糖(TyG)是由甘油三酯和血糖组成的综合指标,与一些疾病有关。目前尚无关于 CYP2C19 多态性、TyG 与早发性脑梗死(CI)(发病年龄≤65 岁)易感性的关联研究报告。

方法

本研究回顾性分析了 2018 年 12 月至 2024 年 3 月期间 1953 例≤65 岁的早发性 CI 患者,并以 1919 例年龄匹配的非 CI 患者作为对照。分析 CYP2C19 多态性、TyG 与早发性 CI 风险的关系。

结果

早发性 CI 患者中高血压和糖尿病的比例高于对照组。早发性 CI 患者的血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和 TyG 水平明显高于对照组(均 P<0.05)。早发性 CI 患者 CYP2C191 等位基因频率(63.3%比 69.6%,P<0.001)较低,CYP2C192 等位基因频率(31.3%比 25.4%,P<0.001)较高。Logistic 回归分析显示,吸烟史(比值比(OR):1.193,95%置信区间(CI):1.002-1.422,P=0.048)、高血压(OR:3.371,95%CI:2.914-3.898,P<0.001)、糖尿病(OR:1.911,95%CI:1.632-2.237,P<0.001)、CYP2C19 中间代谢型(IM)+弱代谢型(PM)表型(OR:1.424,95%CI:1.243-1.631,P<0.001)和血脂异常(OR:1.294,95%CI:1.077-1.554,P=0.006)是早发性 CI 的独立危险因素。

结论

吸烟史、高血压、糖尿病、血脂异常和 CYP2C19 IM+PM 表型与早发性 CI 易感性独立相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bdf/11520391/d0c61f5f151a/12872_2024_4269_Fig1_HTML.jpg

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