Association of Estrogen Receptor-α and Aryl Hydrocarbon Receptor Gene Polymorphisms with Ischemic Stroke in an Egyptian Population: A Pilot Study

Stroke is the second leading cause of death and a major contributor to disability worldwide, with the highest prevalence in developing countries. Ischemic stroke (IS) is a complex disease resulting from genetic and environmental interactions. The present work is a pilot study exploring the association of estrogen receptor-alpha (ESR1) and aryl hydrocarbon receptor (AHR) SNPs with IS in a small Egyptian population of IS patients. Sixty IS patients and 60 matched healthy controls were included in this case-control study. Genotyping of ESR1 PvuII (rs2234693), ESR1 XbaI (rs9340799), and AHR rs2066853 SNPs was performed using real-time PCR. ESR1 PvuII TC and CC genotypes were associated with IS (odds ratio (OR) = 2.821, 95% confidence interval (CI) = 1.204-6.609, p = 0.017, and OR = 9.455, 95% CI = 2.222-40.237, p = 0.002, respectively), and TC genotype in female IS (OR = 4.018, 95% CI = 1.117-14.455, p = 0.033). Additionally, ESR1 XbaI GA and GG genotypes were associated with IS (OR = 2.833, 95% CI = 1.190-6.749, p = 0.019, and OR = 34.000, 95% CI = 6.965-165.980, p < 0.001, respectively), and the AG and GG genotypes in male IS (OR = 3.378, 95% CI = 1.103-10.347, p = 0.033 and OR = 22.8, 95% CI = 2.580-201.488, p = 0.005, respectively) and the GG genotype in female IS (95% CI = 7.259-1115.914, p < 0.001). ESR1 PvuII and XbaI haplotypes C-A, T-G, and C-A increased the risk of IS in both genders, in male IS, and in female IS apart from C-A. The AG genotype of AHR rs2066853 was associated with male IS (OR = 6.900, 95% CI = 2.120-22.457 p = 0.001). ESR1 PvuII, ESR1 XbaI, and AHR rs2066853 SNPs are associated with IS in Egyptians. However, this is a small sample, and the findings should be replicated in a larger population.