The Connotation of Variances in the Risk Predictors, Medications, Homocysteine, and Homocysteine Pathway Gene Polymorphisms with CVA/Stroke

Rizwan Masud; Aleem Ul Haq Khan; Aiman Farogh Anjum; Ghazala Jawwad; Zahid Azeem; Haider Zaigham Baqai; Shoaib Naiyar Hashmi

doi:10.1055/s-0041-1722884

The Connotation of Variances in the Risk Predictors, Medications, Homocysteine, and Homocysteine Pathway Gene Polymorphisms with CVA/Stroke

Glob Med Genet. 2020 Dec;7(4):113-120. doi: 10.1055/s-0041-1722884. Epub 2021 Feb 9.

Authors

Rizwan Masud¹, Aleem Ul Haq Khan², Aiman Farogh Anjum¹, Ghazala Jawwad³, Zahid Azeem⁴, Haider Zaigham Baqai⁵, Shoaib Naiyar Hashmi⁶

Affiliations

¹ Department of Physiology, CMH Kharian Medical College, Kharian, Pakistan.
² Department of Biochemistry, CMH Kharian Medical College, Kharian, Pakistan.
³ Department of Physiology, Rawal Institute of Health Sciences, Islamabad, Pakistan.
⁴ Department of Biochemistry, AJ&K Medical College, Muzaffarabad, AJ&K, Pakistan.
⁵ Department of Medicine, Nafees Medical College, Islamabad, Pakistan.
⁶ Department of Pathology, CMH Kharian Medical College, Kharian, Pakistan.

Abstract

Cerebrovascular accidents (CVAs) are vascular multifactorial, multigenic ailments with intricate genetic, environmental risk influences. The present study aimed to establish affiliation of CVAs/stroke with blood parameters, differences in prescribed drugs consumption, and with differences in homocysteine pathway genes polymorphisms. The participants in study included controls n = 251, transient ischemic attack (TIA) patients n = 16, and stroke cases n = 122, respectively, (total participants, n = 389). The analyzed single nucleotide polymorphisms (SNPs) included C677T(rs1801133), A1298C(rs1801131) of methylene tetrahydrofolate reductase ( MTHFR ), A2756G(rs1805087) of methyl tetrahydrofolate homocysteine methyltransferase/methionine synthase ( MS ), and the A192G(rs662) of paraoxonase 1( PON1 ) genes, all validated by tetra-primer allele refractory mutation system polymerase chain reaction (T-ARMS-PCR). The insertion deletion (I/D; rs4646994) polymorphism in angiotensin converting enzyme ( ACE ) gene was analyzed using routine PCR. All studied traits were scrutinized through analysis of variance (ANOVA), and later through regression analysis. Through ANOVA and multiple comparison, there was association of CVA with serum homocysteine, cholesterol, and with diastolic blood pressure readings. When data was subjected to regression, serum homocysteine and diastolic blood pressure (significant through ANOVA), as well as two additional traits, high-density lipoproteins (HDL), and rs1801133 MTHFR SNP sustained statistical significance and noteworthy odds in relation to CVA and stroke. The ailments affecting cerebral vasculature are mutifactorial, whereby genes, proteins, and environmental cues all exert cumulative effects enhancing CVA risk. The current study emphasizes that SNPs and variation in circulating biomarkers can be used for screening purposes and for reviewing their effects in stroke/CVA-linked risk progression.

Keywords: cerebrovascular accidents; homocysteine; single nucleotide polymorphisms; stroke; transient ischemic attack.

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