M. Benomar

Influence of methionine synthase (A2756G) and methionine synthase reductase (A66G) polymorphisms on plasma homocysteine levels and relation to risk of coronary artery disease.

Background — Elevated plasma total homocysteine (tHcy) is increasingly being recognized as a risk factor for coronary artery disease (CAD) and other defects. Recent genetic studies have characterized molecular determinants contributing to altered homocysteine metabolism. Our objectives were therefore to confirm the relationship of tHcy with CAD and to examine the importance of genetic influence on tHcy in the coronary angiograms and conventional cardiovascular risk factors recorded in 230 subjects.We also determined the genotype frequencies distribution of the A2756G transition of the B12-dependent methionine synthase (MTR) gene and the A66G mutation of the methionine synthase reductase (MTRR) gene. Results — Patients with CAD (n = 151) had significantly higher tHcy concentrations than control subjects (15.49 ± 2.75 μmol/l vs. 11.21 ± 3.54 μmol/l, P < 0.001). Hyperhomocysteinaemia (tHcy ≥15 μmol/l) was a risk factor for CAD [RR = 4.07, 95% CI: 2.21 – 7.47, P < 0.001]. The homocysteine concentrations were significantly different between smokers and non-smokers, at 15.63 ± 3.10 vs. 12.45 ± 3.84 μmol/l, P < 0.05. In addition, smokers with hyperhomocysteinaemia demonstrated a markedly increased risk of CAD (OR = 2.50, 95% CI: 1.67 – 3.32, P < 0.05) compared with non-smokers with normal homocysteine.The 2756G and the 66G allele contribute to a moderate increase in homocysteine levels (P = 0.008 and P = 0.007, respectively), but not to CAD (P > 0.05). Combined MTR and MTRR polymorphisms, the 2756AG + 66AG and the 2756AG + 66GG were the combined genotypes that were a significant risk factor for having hyperhomocysteinaemia (14.4 ± 2.8 μmol/l, OR = 2.75, IC 95% = 1.21 – 6.24, P = 0.016 and 17.9 ± 4.1 μmol/l, OR = 6.28, IC 95% = 1.46 – 12.1, P = 0.021, respectively). Statistic analysis using the UniANOVA test shows that these two polymorphisms have an interactive effect circulating homocysteine levels (P < 0.05). Conclusion — Our data suggest that moderately elevated tHcy levels are prevalent in our population and are associated with an increased risk for CAD. This study provides evidence that the MTR A2756G and MTRR A66G polymorphisms significantly influence the circulating homocysteine concentration. In addition, the MTR and MTRR genes may interact to increase the risk for having hyperhomocysteinaemia.

Thermolabile Methylenetetrahydrofolate Reductase C677T Polymorphism and Homocysteine Are Risk Factors for Coronary Artery Disease in Moroccan Population

Increased plasma total homocysteine (tHcy) levels have been shown to be a risk factor for coronary artery disease (CAD). The common methylenetetrahydrofolate reductase C677T (MTHFR C677T) polymorphism has been reported to be a strong predictor of mild hyperhomocysteinaemia (HHcy). We assessed whether this mutation was associated with increased risk of CAD and plasma levels of tHcy. We also evaluated interactions between this polymorphism, mild elevated tHcy levels and conventional risk factors of CAD. Method. Using PCR-RFLP analysis, we studied the frequency of the C677T genotypes and its effect on CAD and on tHcy concentrations in 400 subjects without and with CAD angiographically confirmed. There were 210 subjects with CAD and 190 subjects without CAD. Results. The frequencies of the C677T genotypes were 53% (59.5% in controls versus 48.1% in cases), 34.8% (32.1 in controls versus 37.1 in cases), and 11.8% (8.4% in controls versus 14.8% in cases), respectively, for 677CC, 677CT, and 677TT. The genotype frequencies were significantly different between case and control groups (P < .05). The 677T allele enhances the risk of CAD associated to HHcy (P < .01). In multivariate analysis models, MTHFR C677T polymorphism effect on CAD was masked by other risk factors. HHcy was only and independently influenced by MTHFR polymorphism and smoking habits, and it is a strong predictor of CAD independently of conventional risk factors. Conclusion. Our data suggest that HHcy is strongly and independently associated to CAD risk increase; and MTHFR C677T polymorphism and smoking habits were the main predictors of tHcy levels. The CAD risk increase is mainly associated with mild HHcy in 677TT, whereas in 677CT and 677CC it is mainly associated with the conventional risk factors.

Valvuloplastie mitrale percutanée chez la femme enceinte : expérience marocaine

Resume La grossesse constitue un facteur de decompensation des cardiopathies valvulaires, plus particulierement du retrecissement mitral (RM). En effet, le RM est la cardiopathie valvulaire la plus frequemment revelee ou aggravee par la gestation. Le traitement chirurgical des cardiopathies valvulaires au cours de la grossesse mettait en jeu le pronostic vital maternel et fœtal. Aussi, la valvuloplastie mitrale percutanee constitue-t-elle, grâce a l’utilisation du ballon d’Inoue et a la reduction actuelle du temps de scopie, une alternative au traitement chirurgical du RM pendant la grossesse. Ce travail rapporte le benefice obtenu apres dilatation mitrale percutanee chez 11 femmes enceintes qui presentaient un RM tres serre decompense. L’indication d’une dilatation mitrale a ete retenue devant la resistance au traitement medical maximal.

Angioplastie transluminale des artères rénales dans l’hypertension artérielle rénovasculaire

Resume Le but de notre travail est d’evaluer le resultat anatomique et fonctionnel de l’angioplastie transluminale de l’artere renale chez les hypertendus porteurs d’une stenose de l’artere renale (SAR). Materiel et methodes. – Vingt-cinq patients hypertendus (8 femmes et 17 hommes d’âge moyen de 42,6 ans et 61,8 ans respectivement) et ayant une SAR hemodynamiquement significative etaient hospitalises au service entre 1997 et 1999. L’origine atheromateuse de la SAR etait retrouvee dans 22 cas (88 %) et fibrodysplasique dans trois cas (12 %). L’angioplastie simple etait realisee chez 11 patients (45,8 %) et la mise en place d’un stent chez 13 patients (54,2 %). Resultats. – Le taux de succes technique de l’angioplastie etait de 96 %. Le resultat anatomique immediat etait meilleur dans le groupe avec stent : 4 % ± 2,4 de stenose residuelle contre 24 % ± 3,9 en cas d’angioplastie simple p Conclusions. – Ces resultats confirment l’interet de l’angioplastie renale dans le traitement de l’hypertension arterielle renovasculaire.