Impact of I/D polymorphism of angiotensin-converting enzyme (ACE) gene on myocardial infarction susceptibility among young Moroccan patients.

OBJECTIVE: Our case-control study aimed to access the potential association of insertion/deletion (I/D) ACE (angiotensin converting enzyme) gene polymorphism with myocardial infarction (MI) risk of occurrence among a sample of Moroccan patients, especially young ones. RESULTS: Distribution of I/D ACE gene variant among cases vs controls, showed that healthy controls carried out higher frequency of wild type allele I compared to cases (23.5% vs 21.79% respectively), when cases were carrying higher frequency of mutant allele D (78.21% vs 76.5% for controls). Patients were-after this- divided into two groups of < 45 and > 55 years of age, to investigate whether or not younger patients carried out higher frequency of the mutant allele D, than older ones. As expected, < 45 years old patients carried out more DD genotype than older ones (68.9% vs 54.6% respectively), and higher frequency of mutant allele D (81.08% vs 75% respectively). Besides, a tendency to a positive association was found under the recessive genetic transmission model (OR [95% CI] = 1.85 [0.93-3.69], P = 0.08), suggesting that the I/D ACE polymorphism may be associated with MI occurrence among younger patients (< 45 years of age).

G2691A and C2491T mutations of factor V gene and pre-disposition to myocardial infarction in Morocco.

Coagulation factor Leiden mutation has been described as a common genetic risk factor for venous thrombosis; however, this mutation was reported to be practically absent in an African population. Recently, a novel non-sense mutation in the gene encoding factor V has been associated with the risk of occurrence of cardio-cerebrovascular diseases such as stroke and venous thrombosis. The aim of the present study was to investigate whether the factor V Leiden (FVL) and C2491T non-sense mutations are associated with the risk of developing myocardial infarction. Genotyping of FVL and C2491T FV was performed using the polymerase chain reaction restriction fragment length polymorphism method on a sample of 100 patients with myocardial infarction as well as 211 controls. In the study population, the frequency of the FVL mutation was practically zero. However, with regard to the C2491T mutation, the TT genotype was associated with an increased risk of myocardial infarction [odds ratio (OR)=3.16, 95% confidence interval (CI): 1.29-7.71, P=0.03]. A significant association between the C2491T FV mutation and the risk of myocardial infarction was identified using recessive (OR=2.74, 95% CI: 1.14-6.58, P=0.04), dominant (OR=1.85, 95% CI: 1.13-3.04, P=0.02) and additive (OR=1.88, 95% CI: 1.25-2.80, P=0.004) models. Furthermore, a positive correlation was found between the presence of the C2491T FV mutation and hypertension (P=0.02), which is associated with myocardial infarction. In conclusion, the results of the present study suggested that the C2491T non-sense mutation of the FV gene may be a risk factor for myocardial infarction in a Moroccan population.

Association of C677T MTHFR and G20210A FII prothrombin polymorphisms with susceptibility to myocardial infarction.

Myocardial infarction (MI) is a common complex pathology, localized in the main leading causes of mortality worldwide. It is the result of the interaction of genetic and environmental factors. The aim of the present study was to investigate the potential association of C677T 5,10-methylenetetrahydrofolate reductase (MTHFR) (rs1801133) and G20210A factor II prothrombin (FII) (rs1799963) polymorphisms with the susceptibility of MI. Following extraction by the standard salting-out procedure, DNA samples of 100 MI patients and 182 apparently healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism using HinfI and HindIII restriction enzymes, respectively. The results show a significant association of the G20210T FII polymorphism with the MI risk. The frequencies of the heterozygote genotype GA, homozygous mutated AA and the G20210A allele was higher among patients compared to controls (GA: 59 vs. 5.5%, P<0.001; AA: 10 vs. 0%, P=0.003; and 20210A: 39.5 vs. 2.7%, P<0.003), suggesting that this polymorphism may be a potential genetic marker for MI. No significant association was observed between the C677T MTHFR and MI occurrence, and there was more heterozygote CT in the patient group compared to the controls. As a multifactorial disease, the development of MI may be the result of numerous factors that influence synergistically its occurrence. Thus, further studies are merited to try to better assess these associations (gene-gene and gene-environment interactions).

Association of G894T eNOS, 4G/5G PAI and T1131C APOA5 polymorphisms with susceptibility to myocardial infarction in Morocco.

BACKGROUND: Myocardial infarction (MI) is a common multifactorial disease. Numerous studies have found that genetic plays an essential role in MI occurrence. The main objective of our case-control study is to explore the association of G894T eNOS (rs1799983), 4G/5G PAI (rs1799889) and T1131C APOA5 (rs662799) polymorphisms with MI susceptibility in the Moroccan population. METHODS AND RESULTS: 118 MI patients were recruited vs 184 healthy controls. DNA samples were genotyped by PCR-RFLP method using MboI, BslI and MseI restriction enzymes respectively for the G894T eNOS, 4G/5G PAI and T1131C APOA5 polymorphisms. Our results show that the G894T eNOS was significantly associated with increased risk of MI under the three genetic transmission models (dominant: OR = 1.64, 95% CI = 1.05-2.58, P = 0.003; recessive: OR = 2.15, 95% CI = 0.74-6.16, P = 0.03; additive: OR = 1.54, 95% CI = 1.06-2.23, P = 0.001). The T1131C APOA5 polymorphism was associated to MI risk in recessive and additive models (OR = 1.53, 95% CI = 0.72-3.2, P = 0.04 and OR = 1.78, 95% CI = 1.26-2.51, P = 0.03 respectively). For the 4G/5G PAI variant, even the cases and controls groups were not in Hardy-Weinberg Equilibrium (HWE), the dominant and additive models show a statistically significant association with MI risk (OR = 7.96, 95%CI = 3.83-16.36, P = 0.01 and OR = 1.96, 95% CI = 1.4-2.72, P = 0.03 respectively). CONCLUSION: Our results suggest that G894T eNOS and T1131C APOA5 polymorphisms may be considered as genetic markers of MI among the Moroccan population. Further studies including larger sample sizes and exploring more genetic associations are needed to confirm our results and to better understand the susceptibility to MI.

[Discordance between mitral valve area (MVA) and pressure gradient in patients with mitral valve stenosis: mean transmitral valve gradient is a severity index or a tolerance index of severity of mitralss valve stenosis?] / Discordance gradient-surface dans le rétrécissement mitral: le gradient moyen transmitral est-il un critère de sévérité ou un indice de tolérance du rétrécissement mitral serré?

Rheumatic mitral valve stenosis (MVS) is a frequent valvulopathy in developing countries. However, industrialized countries have seen the emergence of new etiologies of MVS in recent years, in particular drug-induced and/or toxic valvular regurgitation and stenosis. For this reason, the echocardiographic assessment of MVS and especially the definition of objective diagnostic criteria for severe MVS remains relevant. The objectives are: to determine whether there is a direct causal link between mean transmitral gradient (MTG) and severity of MVS in patients with severe MVS or true severe MVS (primary criterion); to analyze different parameters determining mean transmitral gradient (MTG) (secondary criterion). We conducted a single-center cross-sectional study including all patients with severe or true severe MVS admitted to the Department of Cardiology, University Hospital Ibn Rushd, Casablanca over a period of one year (January 2014-December 2014). We analyzed data from two groups of patients separately: those with a mean transmitral gradient<10 mmHg (group 1) and those with a gradient>10mmHg (group 2). 50 patients with severe or true severe MVS have been included in the study. The average age of our patients was 41.7 years with a female predominance (sex ratio 0,25). 64% of patients had severe MVS and 36% of patients had true severe MVS. 52% (26 patients) had MTG < 10mmHg and 48% (24 patients) had mean gradient> 10mmHg, suggesting no direct correlation between the severity of MVS and MTG (Pearson's correlation coefficient R: -0,137). With regards to dyspnea, 80% of patients of group 1 had stage II NYHA dyspnea (classification system) and 70% of patients of group 2 had stage III NYHA dyspnea (41%) or IV NYHA dyspnea (29%), which means that there was a significant correlation between MTG and the severity of dyspnea (R: 0,586 and p: 0,001). The analytical study of heart rate and the presence of cardiac decompensation compared with mean gradient transmitral showed a significant correlation. Indeed, among patients in group 1, 96% had HR between 60 and 100 bpm and no patient had decompensated heart failure. In group 2, 54% (13 patients) had a HR> 100 bpm and 7 of them (53%) had left decompensated heart failure. The analysis of systolic pulmonary artery pressure conducted in both groups of the study revealed the existence of a statistically significant correlation (R: 0,518 and P: 0,001) between systolic pulmonary artery pressure (SPAP) and MTG. Ventricular rhythm regularity and right ventricular function were not correlated with MTG (R: 0,038 and R: - 0,002 respectively). Mean transmitral gradient is a good indicator of mitral stenosis tolerance but it imperfectly reflects mitral stenosis severity as this depends on several hemodynamic parameters. True severe mitral stenosis may have mean transmitral gradient < 10mmHg, that is why the value of MTG should never be interpreted as single value.