Thromboxane A synthase 1 gene expression and promotor haplotypes are associated with risk of large artery‐atherosclerosis stroke in Iranian population

Large artery atherosclerosis (LAA) is known as an important cause of ischemic stroke (IS), which is a multifactorial disorder. Many candidate genes have been proposed for IS like (TBXAS1) that plays a significant role in LAA stroke pathogenesis. This is the first study on the evaluation of the association of the five single-nucleotide polymorphisms (SNPs) in TBXAS1 promoter region and the level of TBXAS1 transcript with large-artery atherosclerosis stroke. Five SNPs in TBXAS1 genes were investigated in 248 patients with large-artery atherosclerosis stroke and 199 healthy controls in Iranian population in this case-control study through using the high-resolution melting assay. In addition, the relationships between the selected SNPs with alteration of TBXAS1 gene expressions were investigated in terms of blood platelets through the reverse transcription-quantitative polymerase chain reaction. Multivariate logistic analysis with adjustments indicated that rs10256282CC, rs10237429CC, and rs4590360GG genotypes were associated with large-artery atherosclerosis stroke (adjusted odds ratio = 2.804, 2.872, and 2.432, respectively; P < 0.05, q < 0.05). Furthermore, the frequency of CACCG haplotype in the patients was greatly higher than that in the controls (OR = 1.424, 95% CI: 1.071-1.893, P = 0.014738). In addition, TBXAS1 expression was higher in patients compared to the controls (P = 0.021), and individuals with the homozygous mutated genotypes of these SNPs showed a higher expression level compared to other genotype (P < 0.05). In total, our findings indicate a significant association of TBXAS1 gene rs10256282CC, rs10237429CC, and rs4590360GG polymorphisms with large-artery atherosclerosis stroke susceptibility and the level of TBXAS1 expression, which was not previously reported in any population.