Exploring the Association of Genetic Determinants of SIRT1, MTHFR, and MIR146A Gene Polymorphism with the Ischemic Stroke Predisposition: A Case Control Study.

Abstract

Stroke is a major cause of disability and the second greatest cause of death. Both acute and chronic strokes have few available treatment options. Nonetheless, the technique known as genome-wide association study (GWAS) is beginning to significantly influence our comprehension of the genetics of stroke. Therefore, the objective of the present study was to examine the associations between Sirtuin-1 (SIRT1), Methylenetetrahydrofolate reductase (MTHFR), and microRNA 146a (MIR146A) gene variations with ischemic stroke (IS) risk. The study included 200 participants: 100 with clinically confirmed IS and 100 healthy controls. Genotyping of SIRT1 (rs7069102), MTHFR (rs1801131), and MIR146A (rs2910164) was performed using the Amplification-Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR). Blood biochemistry, including lipid profiles and glycemic markers, was determined using spectrophotometric enzymatic colorimetric assays. Statistical techniques employed included the Chi-square test, Fisher’s exact test, and multivariate logistic regression analysis to determine Odds Ratios (OR) and 95% Confidence Intervals (CI). In the codominant model, heterozygosity for MIR146A GC (OR = 1.97, P = 0.040), SIRT1 GC (OR = 1.84, P = 0.044), and MTHFR AC (OR = 2.55, P = 0.0019) was significantly associated with increased stroke susceptibility. In the dominant model, MIR146A (GC + CC), SIRT1 (GC + CC), and MTHFR (AC + CC) genotypes were strongly associated with increased risk (P < 0.05). In the recessive model, MIR146A CC and MTHFR CC genotypes were significantly associated with stroke risk, whereas the SIRT1 CC genotype did not reach statistical significance (P = 0.065). Allelic comparison revealed that the C alleles of MIR146A, SIRT1, and MTHFR were all strongly associated with stroke predisposition (P < 0.05). We conclude that there is a possible strong association between the SIRT1 rs7069102 C > G, MTHFR rs1801131 C > A and MIR146A rs2910164 C > G gene variants and ischemic stroke susceptibility. To the best of our knowledge, it is the first study to highlight the association between these genetic variations and the predisposition of stroke in our populations. Large-scale case–control studies in the future are required to confirm these results. These results, when confirmed, can be used in genetic testing for the screening and prognosis of stroke.