Methylenetetrahydrofolate Reductase Polymorphism and Premature Coronary Artery Disease

Zaghloul, Ahmed; Iorgoveanu, Corina; Desai, Aakash; Balakumaran, Kathir; Chen, Kai

doi:10.7759/cureus.5014

“…There are over 20 gene polymorphisms known for the MTHFR enzyme, where C677T is among the most studied ones. Although they are associated with different health issues, C677T is found to have the strongest association with CAD [6]. COVID-19 infection has been connected to prothrombotic conditions such as acute MI in patients, especially in the 1 st month of the primary infection [7], [8], [9] A recent study also demonstrated the longterm cardiovascular events post-COVID-19 infections, beyond the first 30 days after infection, building a cohort of 153,760 individuals with COVID-19 and comparing them to two sets of control cohorts.…”

Section: Introductionmentioning

confidence: 94%

A Curious Case of Acute STEMI in a Young Patient; Things are Not Always What They Seem

Vraynko,

Zafirovska,

Dimitrovska

et al. 2023

SEE J Cardiol

0

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BACKGROUND: Acute myocardial infarction (MI) is a rare occurrence in patients under 40 years of age without positive family history for coronary artery disease (CAD). Genetic conditions as inherited thrombophilia can lead to a hypercoagulable state, resulting in thromboembolic events and arterial thrombosis. CASE SUMMARY: We present a case of a 35-year-old male patient who presented to the emergency room with an inferior MI after a strenuous cycling exercise. An urgent coronary angiography showed thrombotic formations in the right coronary artery without atherosclerotic plaques. Plain old balloon angioplasty and thrombus aspiration were performed, which was followed by GP IIb/IIIa inhibitor infusion and unfractionated heparin for 24 h. From past medical history, the patient had COVID-19 like symptoms 20 days before the event and had his first dose of anti- COVID vaccine 2 weeks prior. After additional testing, molecular genetic analysis results revealed the patient to be heterozygous for factor V Leiden (FVL) and homozygous for methylenetetrahydrofolate reductase C677T gene mutation. The patient was discharged on direct oral anticoagulant and antiplatelet therapy. After 1-year follow-up, he had no symptoms or recurrent cardiovascular events. CONCLUSION: Inherited thrombophilia is а significant risk factor for CAD and performing genetic testing in younger patients with a cardiovascular event and plays an important role for adequate treatment and prophylaxis from recurrent complications. The use of oral anticoagulation for prophylaxis is shown to be effective in these patients. However, further studies are needed to prove their exact role and duration of treatment.

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“…Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism, providing a methyl group for Hcy remethylation into methionine and maintaining the normal levels of Hcy in the body [ 11 ]. Mutations of the MTHFR gene decrease MTHFR enzyme activity that prevents Hcy remethylation and increases Hcy levels in plasma [ 11 , 12 ]. The MTHFR gene has at least two functional polymorphisms, 677T and 1298C.…”

Section: Introductionmentioning

confidence: 99%

Explore the Role of the rs1801133-PPARG Pathway in the H-type Hypertension

Liang

¹

,

He

²

,

Gao

³

et al. 2022

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Both rs1801133 mutation on Methylenetetrahydrofolate reductase (MTHFR) gene and transcription factor peroxisome proliferator-activated gamma (PPARG) have been associated with plasma homocysteine (Hcy) levels and hypertension. However, their role in H-type hypertension remains unclear. In this study, we first tested the association between rs1801133 genotypes and Hcy level in H-type hypertension using clinical profiles collected from 203 patients before and after the treatment using enalapril maleate and folic acid tablets (EMFAT). Then, we constructed a literature-based pathway analysis to explore the role of the rs1801133-PPARG signaling pathway in H-type hypertension and its treatment. Although presented similar blood pressure, the patients with TT genotype of rs1801133 were much younger ( p value <0.05) and significantly higher in Hcy levels ( x 2 = 6.11 and p < 0.005 ) than that in the CC and CT genotype groups. Pathway analysis showed that T-allele of rs1801133 could inhibit the expression of PPARG through the downregulation of folate levels and upregulation of Hcy levels, which increased the risk of hypertension and hyperhomocysteinemia. Treatment using EMFAT led to similarly decreased Hcy levels for all patients with different genotypes ( x 2 = 86.00 ; p < 0.36 ), which may occur partially through the activation of PPARG. Moreover, even after treatment, the patients with TT genotype still presented significantly higher Hcy levels ( x 2 = 7.87 and p < 0.001 ). Our results supported that rs1801133 mutation could play a role in H-type hypertension, which might be partially through the downregulation of PPARG. Moreover, PPARG might also be involved in treating H-type hypertension using EMFAT.

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“…16 The most common mutated form of MTHFR is C677T, whereas the mutant allele TT can increase the probability of a high Hcy level. [17][18][19] The previous studies have been done for detecting the association of Hcy enzyme gene polymorphisms and CHD with contradictory results. [20][21][22] Moreover, scanty reports are available from the Indian scenario as the majority of studies from Asia are confined to China, Japan, and the Sri Lankan population.…”

Section: Introductionmentioning

confidence: 99%

Study on the polymorphism of methylenetetrahydrofolate reductase C677T gene as the genetic predisposition of congenital heart disease in North Indian population

Panja

¹

,

Abhinay

²

,

Pakhira

³

2022

Asian J Med Sci

0

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Background: The etiology of congenital heart disease (CHD) is still not known properly. The variant alleles in the methylenetetrahydrofolate reductase (MTHFR) C677T gene help in elevating the serum homocysteine level which is an independent predisposing factor for generating CHD. Aims and Objectives: The aim of the present study was to analyze the role of polymorphism of MTHFR C677T gene polymorphisms in CHD patients of Varanasi, Uttar Pradesh, North India. Materials and Methods: The present study included 36 unrelated CHD patients along with their parents. At the same time, 40 healthy control samples were included in the study. MTHFR 677 C>T genotype was identified by polymerase chain reaction followed by restriction digestion restriction fragment length polymorphism mechanism. Results: There was a significant difference observed in MTHFR C677T gene polymorphism between the cases and controls (P<0.001). Among the different etiological factors, increased maternal age, family history, and teratogens are the major ones. Maternal MTHFR C677T genotype and periconceptional folate intake have important ascription toward CHD formation. Conclusion: The results designate that MTHFR C677T polymorphism has a substantial association with the development and progression of CHDs. Folate supplementation might be the probable management strategy for reducing the risk of CHDs as maternal MTHFR C677T polymorphism has an important contribution.

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Methylenetetrahydrofolate Reductase Polymorphism and Premature Coronary Artery Disease

Cited by 9 publications

References 13 publications

A Curious Case of Acute STEMI in a Young Patient; Things are Not Always What They Seem

A Curious Case of Acute STEMI in a Young Patient; Things are Not Always What They Seem

Explore the Role of the rs1801133-PPARG Pathway in the H-type Hypertension

Study on the polymorphism of methylenetetrahydrofolate reductase C677T gene as the genetic predisposition of congenital heart disease in North Indian population

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