GENETIC DETERMINANTS OF HYPERHOMOCYSTEINEMIA IN ATHEROSCLEROSIS
Journal Title: Indian Journal of Clinical Biochemistry - Year 2006, Vol 21, Issue 2
Abstract
ABSTRACT Hyperhomocysteinemia (Hhcy) is an independent risk factor for the development of atherosclerosis. The mechanisms by which HHcy promotes cardiovascular disease may be due to activation of pro-inflammatory factors, endoplasmic reticulum (ER) stress and oxidative stress. We aimed to study (i) gene mutations that cause HHcy. (ii) Estimation of inflammatory marker like ultrasensitive C-reactive proteins (hs-CRP) and total antioxidant levels (iii) determination of Hcy– dependent gene expression in vivo. 25 HHcy patients and 25 healthy controls were taken for this study. Mutation detection in MTHFR, CBS, MS and eNOS gene was by PCR-based restriction enzyme analysis and subsequently expression study was carried out by Reverse Transcriptase PCR and cloning technique. A significant association of HHcy with MTHFR (C677T) and MS (A2756G) genotype was observed (p< 0.05). There was no association of Hhcy and eNOS genotype. The Hhcy patients, showed no expression of the ER stress gene, GRP78 in lymphocytes. Our study showed no effect of Hcy on the CD18 gene (pro- inflammatory pathway) expression, but a significant association of tHcy and hs-CRP levels in HHcy grp (t=2.28, p< 0.05). This shows that HHcy induces inflammatory response, which could lead to tissue injury in the pathogenesis of the atherosclerotic process. Our findings show higher mRNA expression of manganese superoxide dismutase (Mn SOD) in HHcy group as compared to the control group .The Total Antioxidant Status (TAS) estimated was found to be significantly lower in the HHcy group as compared to healthy normals (t=4.8, p
Authors and Affiliations
Farah , Eghlim, Tester Ashavaid, Kappiareth Nair
Keywords
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