Genetic Variants That Participate In Oxidation Processes And/Or Oxidative Stress And Are Associated With Atherosclerosis

Ingrida Pepalyte, Zita Aušrele Kučinskiene, Kristina Grigalionienė, Žaneta Petrulionienė, Vilma Dženkevičiūtė, Loreta Bagdonaitė, Vaidutis Kučinskas

Abstract


Motivation. Our previous study showed differences in the atherosclerosis phenotype between Lithuanian and Swedish men that could be influenced by complementary factors, namely oxidation processes and/or oxidative stress. The goal of this study was to evaluate the mainstream biological pathways inducing and maintaining the atherosclerotic process by analyzing genetic biomarkers particularly in inflammatory and metabolic pathways where the main focus is laid on the oxidation process.

Methods. There were 32 families recruited for the study and clinical as well as biochemical analyses were performed. For genetic analysis 150 SNPs in 89 genes were selected in order to construct a micro-array based on Arrayed Primer Extension (APEX) genotyping technology. Genotyping was carried out in 28 families and transmission disequilibrium test (TDT), sibling-TDT (S-TDT), and combined analysis were performed.

Results. Clinical and biochemical analysis revealed that probands with premature CAD were more likely to have diabetes mellitus, arterial hypertension, dyslipidemia and were male with high body mass index. Genetic analysis showed six SNPs statistically significantly associated with the atherosclerosis phenotype in the candidate genes ITGA2, IL1B, ALOX5A, OR13G1, MMP9 and NFKB1. These genes belong to different biological pathways: trombocyte adhesion and vessel damage, inflammation response, cholesterol and lypoxygenase metabolic pathway and nutrition.

Conclusions. Generalized clinical, biochemical, bioinformatical and candidate genes’ association results support our hypothesis and indicate that the oxidation process may be of key importance in the formation of atherosclerosis.


Keywords


Genotyping Technology, Association Analysis, Oxidation Process, Premature CAD, Transmission Disequilibrium Test.

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DOI: http://dx.doi.org/10.12955/emhpj.v3i0.347

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