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Homocysteine concentration in coronary artery disease and severity of coronary lesions
Zhi Luo1, Kai Tang1, Gang Huang1
1Department of Cardiology, Suining Central Hospital, Suining, Sichuan, China.
Insights
The MTHFR rs1801133 variant increases coronary artery disease (CAD) risk and lesion severity, partly via elevated homocysteine levels. Hyperhomocysteinemia predicts severe CAD in the Chinese Han population.
Area of Science:
- Genetics
- Cardiology
- Biochemistry
Background:
- The 5,10-methylenetetrahydrofolate reductase (MTHFR) rs1801133 variant's role in coronary artery disease (CAD) may be mediated by cardiometabolic factors.
- Previous research suggests a potential link, necessitating further investigation.
Purpose of the Study:
- To verify the hypothesis that the MTHFR rs1801133 variant impacts CAD risk and severity through cardiometabolic alterations.
- To investigate the association between the rs1801133 variant, homocysteine levels, and CAD characteristics in the Chinese Han population.
Main Methods:
- A case-control study involving 430 CAD patients and 216 controls.
- Genotyping of the rs1801133 variant using PCR-RFLP.
- Assessment of coronary lesion severity by vessel number and stenosis extent.
- Biochemical analysis of homocysteine, lipids, and inflammatory markers.
Main Results:
- The rs1801133 T allele was associated with increased homocysteine levels and higher CAD risk.
- The TT genotype correlated with multiple vessel lesions, while CT genotype showed altered SBP, LDL-C, hs-CRP, and APOA1 levels in male CAD patients.
- Hyperhomocysteinemia demonstrated high predictive value for CAD severity and multiple vessel lesions.
- Homocysteine, rs1801133, age, smoking, BMI, Lp(a), and hs-CRP were identified as independent CAD risk factors.
Conclusions:
- The MTHFR rs1801133 variant contributes to CAD risk and lesion severity in the Chinese Han population, partly mediated by elevated homocysteine.
- Hyperhomocysteinemia is a significant predictor of severe coronary artery disease.
Abstract:
Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.
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