common mutation in methylene tetrahydrofolate reductase gene, inflammation and atherosclerosis in chronic renal failure

ABSTRACT

Accelerated atherosclerosis is the major cause of mortality in patients on chronic haemodialysis [HD]. Inflammation and endothelial activation or dysfunction might be the major factors leading to high cardiovascular mortality rate in HD patients. Also, C667T mutation of methyltetrahydrofolate reductase [MTHFR] might be associated with accelerated athcrosclerosis. The present study was designed to clarify the role of inflammation, endothelial activation or dysfunction and genotyping of MTHFR enzyme which affect the level or homocysteine and their relation to carotid artery intima-media thickness [CIMT] as an indicator of atherosclerosis. Forty four [44] chronic haemodialysis [HD] patients and 40 healthy subjects were included in the study. Serum highly sensitive C reactive protein [hs-CRP] and IL-6 were measured as inflammatory markers, soluble vascular cell adhesion molecule-1 [sVCAM-1] was measured as a marker of endothelial activation and dysfunction. Common carotid intimal media thickness [CC-IMT] was assessed by carotid artery ultrasonography. genotyping of MTHFR enzyme which affect the level of homocysteine was analyzed by PCR RFLIP technique. Chronic HD patients had elevated levels of inflammatory markers [hs-CRP and IL-6], enhanced endothelial activation or dysfunction demonstrated by elevated VCAM-1 as compared by healthy controls. Haemodialysis patients had significantly higher CC-IMT levels. There is a significant positive correlation between inflammatory cytokines [hs-CRP and IL-6], and each with VCAM-1 and CC-IMT There is no difference in the genotype of C667T MTHFR found between patients and controls, but this mutation especially the TT genotype is associated with development of atherosclerosis as indicated by the increase of CC-IMT