Homocysteine and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Tunisian patients with severe coronary artery disease |
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Authors: | Lakhdar Ghazouani Nesrine Abboud Nabil Mtiraoui Walid Zammiti Faouzi Addad Haitham Amin Wassim Y Almawi Touhami Mahjoub |
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Institution: | (1) Research Unit of Haematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia;(2) CHU Fattouma Bourguiba, Monastir, Tunisia;(3) Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, P.O. Box 22979, Manama, Bahrain |
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Abstract: | Elevation in homocysteine and methylenetetrahydrofolate reductase (MTHFR) gene variants, C677T and A1298C, have been linked
with atherothrombosis. However their exact contribution to coronary artery disease (CAD) remains controversial. Moreover,
data from Tunisian patients are scarse. We examined the association of MTHFR C677T and A1298C, and changes in plasma homocysteine
in 352 Tunisian patients with angiographically-demonstrated CAD, and 390 age and gender-matched healthy subjects. Significantly
higher frequency of 677T allele and homozygous 677T/T genotype were seen in patients vs. control subjects; the distribution
of A1298C alleles and genotypes being comparable in the two groups. Specific MTHFR haplotypes comprising 677C/1298A (P < 0.001) and 677T/1298A (P < 0.001) were negatively and positively associated with CAD, respectively. Plasma homocysteine concentration was significantly
higher in 677T/T genotype with respect to 677C/C and 677C/T genotypes in patients and controls, but homocysteine levels were
generally comparable between both groups. Univariate analysis identified 677T/1298A (P = 0.033) haplotype to be positively associated with CAD, which remained significant by multivariate analysis after adjusting
for a number of covariates (P = 0.038). MTHFR C677T, but not A1298C SNPs, is associated with CAD and with elevated homocysteine levels in a Tunisian population.
The negative and positive association of the 1298A allele with CAD being indicative of a neutral (absent) effect of the A1298C
SNP on disease pathogenesis. |
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Keywords: | Homocysteine Coronary artery disease Mehylenetetrahydrofolate Reductase Mutation |
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