Table 1 Amino acids substitution, normal genetic function, chromosomal location, and effects on genetic expression of the five studied polymorphisms
Gene/polymorphism/amino acid substitution | Chr | Function of encoded protein * | Effect of polymorphism |
|---|---|---|---|
MTHFR (methylenetetrahydrofolate reductase)/rs1801133 (C677T)/Ala > Val | 1 | MTHFR is an enzyme involved in folate metabolism. It reduces 5, 10-MTHF to 5-MTHF, which donates a methyl group for the conversion of homocysteine to methionine | The C677T mutation leads to enzyme dysfunction. This contributes to hyperhomocysteinemia and reduces folate levels (Raghubeer and Matsha, 2021) |
MTRR (methionine synthase reductase)/rs1801394 (A66G)/Ile > Met | 5 | MTRR is another enzymatic member of folate metabolism by regenerating methionine synthase to a functional state. | A66G substitution adversely influences the enzyme activity, and thus, it is considered as a genetic risk factor for hyperhomocysteinemia [24] |
MTR (methionine synthase)/rs1805087 (A2756G)/Asp > Gly | 1 | MTR enzyme, also known as cobalamin-dependent methionine synthase, catalyzes the final step in methionine biosynthesis from homocysteine in folate metabolism cycle | 2756A > G reduces enzymatic activity and causes higher homocysteine levels and DNA hypomethylation [20] |
AGT (angiotensinogen)/rs699 (T704C)/Met > Thr | 1 | Angiotensinogen is part of renin–angiotensin system. It is cleaved by renin in response to lowered blood pressure. It is involved in maintaining blood pressure, body fluid, and electrolyte homeostasis | ThrThr235 genotype is known to be associated with higher genetic expression and thus increased AGT concentration [1] |
VEGFA (vascular endothelial growth factor A)/rs2010963 (634C > G)/polymorphism located in the 5′-untranslated region of the gene | 6 | Heparin-binding protein, which exists as a disulfide-linked homodimer. This growth factor induces proliferation and migration of vascular endothelial cells and is essential for both physiological and pathological angiogenesis | Mutant allele (G) is associated with lower level of VEFGA genetic expression. Several studies have shown that this polymorphism could affect angiogenesis, which leads to placental insufficiency and endothelial dysfunction [23] |