The influence of genetic and environmental factors on plasma homocysteine concentrations in a population at high risk for coronary artery disease

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Abstract
Background: Elevated plasma total homocysteine (tHcy) predisposes to vascular disease and results from interactions between genetic and nutritional factors. MTHFR C677T increases tHcy in association with low folate. CBS 844ins68 lowers tHcy and negates the raising effect of MTHFR C677T in healthy subjects, but it is unclear if this is the case in subjects at high risk of vascular disease. This study examines the effect on plasma tHcy of interactions between these polymorphisms in an at-risk group. Methods: Blood samples were collected from 376 subjects at increased risk of coronary artery disease. Plasma tHcy and vitamin B6 were measured by HPLC and red cell folate and serum vitamin B12 were measured by immuno-luminometric assay. MTHFR C677T and CBS 844ins68 status was established by standard PCR techniques. Results: MTHFR TT predisposed to hyperhomocysteinaemia; this was increased in the presence of low folate ( P12 ( P12 ( r= -0.26, P6 ( r= -0.25, P677T and CBS 844ins68. Discussion: In this population at high risk of coronary artery disease, plasma tHcy was determined by vitamin status. This was exacerbated by the MTHFR C677T mutation. CBS 844ins68 did not influence tHcy and did not negate the tHcy-raising effect of MTHFR C677T.

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