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Homocysteine and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Tunisian patients with severe coronary artery disease

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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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Authors and Affiliations

  1. Research Unit of Haematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia

    Lakhdar Ghazouani, Nesrine Abboud, Nabil Mtiraoui, Walid Zammiti & Touhami Mahjoub

  2. CHU Fattouma Bourguiba, Monastir, Tunisia

    Faouzi Addad

  3. Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, P.O. Box 22979, Manama, Bahrain

    Haitham Amin & Wassim Y. Almawi

Authors
  1. Lakhdar Ghazouani
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  2. Nesrine Abboud
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  3. Nabil Mtiraoui
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  4. Walid Zammiti
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  5. Faouzi Addad
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  6. Haitham Amin
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  7. Wassim Y. Almawi
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  8. Touhami Mahjoub
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Correspondence to Wassim Y. Almawi.

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Ghazouani, L., Abboud, N., Mtiraoui, N. et al. Homocysteine and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Tunisian patients with severe coronary artery disease. J Thromb Thrombolysis 27, 191–197 (2009). https://doi.org/10.1007/s11239-008-0194-1

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  • DOI: https://doi.org/10.1007/s11239-008-0194-1

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