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  • Title: Thromboxane A synthase 1 gene expression and promotor haplotypes are associated with risk of large artery-atherosclerosis stroke in Iranian population.
    Author: Ramazi S, Heydari-Zarnagh H, Goudarzian M, Khalaj-Kondori M, Bonyadi M.
    Journal: J Cell Biochem; 2019 Sep; 120(9):15222-15232. PubMed ID: 31026093.
    Abstract:
    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.
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