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The Correlation of MTHFR SNPs, Homocysteine, and Conventional Risk Predictors with Coronary Artery Disease

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Abstract

Arterial thromboembolic disease affects coronary vasculature and has an exhaustive list of etiologies. The aim of the present study was to investigate the effects of genetic variants in homocysteine pathway genes, homocysteine levels, and other modifiable and non-modifiable conventionally allotted risk factors for coronary artery disease. Study was retrospective case control study, comprised 404 participants (controls, n = 179, ischemic heart disease (IHD) patients, n = 89, and myocardial infarction (MI) cases, n = 136, respectively). Single nucleotide polymorphisms (SNPs); rs1801133, rs1801131 in methylenetetrahydrofolate reductase ‘MTHFR’ gene, rs1805087 in methyl tetrahydrofolate homocysteine methyltransferase ‘MTR’ gene, and rs662 in paroxanse1 ‘PON1’ gene, rs4646994, angiotensin converting enzyme ‘ACE’ insertion/deletion (I/D) polymorphism were resolved employing conventional, and by tetra primer allele refractory mutation system polymerase chain reaction (PCR). ANOVA association testing revealed that homocysteine, cholesterol, creatinine, triglyceride levels, age, family history of CAD, and polymorphisms in MTHFR and PON1 related to coronary artery disease. The post HOC analysis also maintained significance differences in the control, ischemic heart disease and case groups respectively. The regression analysis failed to maintain statistical significance for creatinine, triglycerides, age, and rs662 PON1 polymorphism, whereby, serum homocysteine, cholesterol, family history, and rs1801133/rs1801131 MTHFR SNPs maintained statistical significance. The results from the present study provide hint into interlaced nature of traditional and novel risk factors in the causation of arterial disease and an insight into their shared detrimental effects in affecting the coronary vasculature.

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ACKNOWLEDGMENTS

The authors are grateful to Prof Dr I.J, Kullo, Dr Keyue Ding, Dr Wasim, Dr Asad, and Dr Tariq for samples, for valuable comments, and help in manuscript.

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Authors and Affiliations

  1. CMH Kharian Medical College, Next to CMH, Kharian Cantt, 49600, Kharian, Punjab, Pakistan

    R. Masud & A. U. H. Khan

  2. Al-Nafees Medical College, 44000, Farash Town, Islamabad, Pakistan

    H. Z. Baqai

  3. College of Medicine, King Faisal University, 31982, Al-Ahsa, Kingdom of Saudi Arabia

    A. Iqbal

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  1. R. Masud
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Statement of compliance with standards of research involving humans as subjects. The Pakistan Medical Research Council, Islamabad and Institutional Review Board CMH Kharian Medical College approved the study. All the participants provided written informed consent for use of data and samples for the current research project. The institutional ethical standards were rigorously exercised and all experiments were carried out under the Helsinki Declaration guidelines.

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Masud, R., Khan, A.U., Baqai, H.Z. et al. The Correlation of MTHFR SNPs, Homocysteine, and Conventional Risk Predictors with Coronary Artery Disease. Russ J Genet 57, 1328–1336 (2021). https://doi.org/10.1134/S1022795421110077

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