Sonographic evaluation of atherosclerosis burden in carotid arteries of ischemic stroke patients and its relation to paraoxonase 1 and 2, MTHFR and AT1R genetic variants

Abstract

Objective: Common variants of the Paraoxonase (PON), 5-Methyl-Tetrahydrofolate-Reductase (MTHFR) and Angiotensin-II receptor 1 (AT1R) genes have been associated with ischemic stroke (IS) risk. Moreover, carotid atherosclerosis is a common cause of IS. The aim of this study is to explore whether variants in these genes associate with the severity of ultrasonographic determined atherosclerosis assessed in carotid arteries. Patients and methods: Etiologic subtype of cerebral ischemia was determined according to the TOAST classification. Genotypes were detected by PCR and restriction analysis. An ultrasonographic supra-aortic trunks study was performed to all patients to assess their atherosclerotic involvement based on predefined criteria. Results: In IS patients, none of the analyzed gene distributions differed concerning the stenosis degree. Nevertheless, a trend was observed for the rs662 and rs7493 variants of the PON1 and PON2 genes respectively. When evaluated the results based on different inheritance models, a significant contribution of rs7493 variant according to a dominant (or = 2.397, 95\% CI (1.001-5.376); p = 0.045) and log-additive inheritance forms (or = 1.85, 95\% CI (1.07-3.2); p = 0.03) was observed. only rs7493 reached statistical significance (p = 0.013), when genotype distribution was analyzed according to carotid intima-media thickness (cIMT) and remain significant in multivariate logistic regression analysis (or = 2.66, 95\% CI (1.1 to 6.4); p = 0.03). Conclusion: In IS patients of the north area of the Gran Canaria island the PON2 (rs7493) gene variant associates with a worse ultrasonographic profile. Conversely, the Cys311Cys homozygosis of the rs7493 variant was also related to a better ultrasonographic profile in our study.