Effect of CYP2C9 and VKORC1 Gene Polymorphism on Warfarin Stable Dose and Myocardial Injury After Heart Valve Replacement in Qiandongnan Region
10.3870/j.issn.1672-0741.25.01.006
- VernacularTitle:黔东南地区CYP2C9、VKORC1基因多态性对心脏瓣膜置换术后患者华法林稳定剂量及心肌损伤影响的临床研究
- Author:
Rong YANG
1
;
Shaodong NING
1
;
Jun YANG
1
Author Information
1. 贵州医科大学第二附属医院心胸外科,凯里 556000
- Publication Type:Journal Article
- Keywords:
CYP2C9;
VKORC1;
gene polymorphism;
heart valve replacement;
myocardial injury
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(4):552-560
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of CYP2C9 and VKORC1 gene polymorphism on warfarin stable dose and myocardial injury in patients after heart valve replacement in Qiandongnan region.Methods Clinical data of 110 patients in Qi-andongnan who underwent heart valve surgery at Guizhou Medical University's Second Affiliated Hospital's Cardiothoracic De-partment(form November 2019 to October 2024)were collected.According to CYP2C9*3 genotype,patients were divided into wild type(AA type)and mutant type(AC type and CC type),and VKORC1-1639G>A genotype was divided into wild type(GG type)and mutant type(GA type and AA type).Levene variance homogeneity test was performed first to compare warfarin dose between different genotypes and INRcompliance timebetween groups.The factors affecting the stable dose of warfarin werean-alyzed by hierarchical regression.BP neural network model is used for risk prediction.Generalized linear mixed effects model(GLMMs)was used to analyze the relationship between CYP2C9 and VKORC1 gene status and postoperative myocardial inju-ry.Results The distribution of all genes was consistent with Hardy-Weinberg genetic balance(both P>0.05).CYP2C9*3 and VKORC1-1639G>A gene status were significantly different from atrial fibrillation,myocardial injury,thrombosis and hemor-rhage,and combined drugs(amiodarone,rifampicin,phenobarbital,voriconazole)(all P<0.05).The compliance rate(TTR)and warfarin stable dose of warfarin anticoagulation therapy for CYP2C9*3 genotype AA were significantly higher than that of genotype AC(both P<0.01),and the INR compliance time was significantly lower than that of genotype AC(both P<0.01).The warfarin stable dose and INR reach time of VKORC1-1639G>A genotype GG+GA were significantly higher than geno-type AA(both P<0.01),and TTR was significantly lower than genotype AA(both P<0.01).Stratified regression analysis showed that CYP2C9,VKORC1,age,amiodarone,BSA,BMI and gender had significant effects on warfarin stable dose(all P<0.05).BP neural network model construction showed that CYP2C9 and VKORC1 had the highest contribution to model classifi-cation,followed by amiodarone,BSA,BMI,gender and age.The model verification results showed that the accuracy was 93.54％,the sensitivity and specificity were 85.62％and 95.89％,respectively.The positive predictive value was 94.23％,the negative predictivevaluewas 93.15％,and the ROC AUC fitting of thepredictionmodelwas 0.958.The levels of cTnI,CK-MB and hs-CRP in CYP2C9*3 and VKORC1-1639G>A mutant patients were significantly higher than those in wild-type patients(P<0.05).GLMMs model analysis showed that CYP2C9 and VKORC1 gene mutations were still statistically associated with the risk of postoperative myocardial injury regardless of adjustment factors(P<0.01).Conclusion The CYP2C9 * 3 and VKORC1-1639G>A gene polymorphisms in patients who underwent heart valve replacement surgery in Qiandongnan area sig-nificantly affect the stable dose of warfarin and the rate of achieving anticoagulation targets.Moreover,the mutant genes are closely related to the increase in postoperative myocardial injury indicators and the increased risk.
