Tarek A. Abd El-Aziz

The relationship between paraoxonase1-192 polymorphism and activity with coronary artery disease.

OBJECTIVE We tested the association between PON1 polymorphism, PON1 activity, oxidative susceptibility of LDL and coronary artery disease in Egyptians. METHODS PON1 polymorphism, serum PON1 activity, lipoprotein oxidation susceptibility and lipid profile were measured. RESULTS Levels of HDL and paraoxonase activity were significantly decreased in CAD patients compared to control group, and in patients with three vessels compared to those of single or two vessels disease. High-activity allele (R) has a more atherogenic lipid profile than for the low activity allele (Q). PON1 RR genotype has nine fold risks to develop CAD in Egyptians while those with PON1 QR genotype have four fold risks. CONCLUSION The PON1 activity is lower in subject with CAD and there is a significant relationship between activity of PON1 and the severity of coronary atherosclerosis. Also, we provide evidence of a significant association between R allele of the PON1 polymorphism and the development of coronary artery disease.

Renin-angiotensin system genes polymorphism in Egyptians with premature coronary artery disease.

Genetics polymorphism of the renin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and associated with coronary artery disease (CAD). We aimed to investigate the association between the RAS genes and premature CAD (PCAD) in Egyptians. 116 patients with PCAD, 114 patients with late onset CAD and 119 controls were included in the study. Angiotensin converting enzyme (ACE), angiotensin II receptor type 1 (ATR1) and angiotensinogen (AGT) genes polymorphisms were analyzed by polymerase chain reaction (PCR). We found that ACE DD, AGT TT and ATR1 CC increased the risk of PCAD by 2.7, 2.8 and 2.86 respectively). Smoking, hypertension, diabetes, total cholesterol, triglycerides and LDL cholesterol were independent risk factors for the development of PCAD. We conclude that the ACE DD, AGT TT and ATR1 CC genotypes may increase the susceptibility of an individual to have PCAD. The coexistence of CAD risk factors with these risky RAS genotypes may lead to the development of PCAD in Egyptian patients.

Increased risk of premature coronary artery disease in Egyptians with ABCA1 (R219K), CETP (TaqIB), and LCAT (4886C/T) genes polymorphism

BACKGROUND Epidemiological studies have shown a strong inverse relationship between high-density lipoprotein (HDL) cholesterol (HDLc) levels and coronary artery disease (CAD), and a low concentration of plasma HDLc is considered an independent risk factor for premature atherosclerosis. Mutations in ATP-binding cassette A1 transporter (ABCA1), cholesteryl ester transfer protein (CETP), and lecithin: cholesterol acyltransferase (LCAT) reduce HDLc in humans. OBJECTIVE To date, no study had tested the association between these polymorphisms and premature CAD (PCAD) in the Egyptian population. Here we searched for ABCA1 (rs2230806), CETP (rs708272), and LCAT (rs5923) mutations in the Egyptian population and investigated the possible association between these gene polymorphisms and PCAD. We aimed to investigate the association between ABCA1, CETP, and LCAT gene polymorphisms and PCAD in Egyptians. METHODS A total of 235 Egyptians-116 with documented PCAD (PCAD group) and 119 controls-were enrolled in the study. RESULTS Mutation carriers with low HDLc had an elevated risk of PCAD (odds ratio [OR] = 11.38 for ABCA1 mutation carriers, P = .000; OR = 5.41 for CETP mutation carriers, P = .000; OR = 5.92 for LCAT mutation carriers, P = .000). Moreover, mutations in ABCA1, CETP, and LCAT were significantly associated with hyperlipidemia in this study. CONCLUSION These observations show that the R allele of ABCA1, the B1 allele of CETP, and the T allele LCAT genes are associated with PCAD in Egyptians. They have more considerable effect on patients with low HDLc.

Leptin, leptin gene and leptin receptor gene polymorphism in heart failure with preserved ejection fraction

Heart failure with a normal ejection fraction (HFNEF) is common in obesity and coronary artery disease (CAD). Both ischemia and reperfusion induce leptin (LEP) and leptin receptor (LEPR) gene expression. We aimed to investigate the possible associations of serum leptin, leptin gene and leptin receptor gene polymorphism with HFNEF in patients with CAD. 100 Egyptian CAD patients with HFNEF and 100 healthy subjects (the control group) were genotyped for LEP and LEPR polymorphism. Leptin levels were measured. Serum leptin levels were significantly increased in patients compared to the control group. There was a significant increase in the leptin gene (AA genotype) and the leptin receptor gene (RR genotype) in HFNEF patients compared to the control group. Leptin levels, leptin gene (AA genotype) and LEPR (RR genotype) were more associated with NYHA III than with NYHA I and II. We thus concluded that HFNEF is associated with increased serum leptin levels, and the LEP AA genotype or LEPR RR genotype carries at least a threefold increased risk of developing HFNEF.

Association of lipoprotein lipase and apolipoprotein C-III genes polymorphism with acute myocardial infarction in diabetic patients

Lipoprotein lipase (LPL) and Apolipoprotein C-III (APOC-III) play an important role in lipid metabolism. The aim of this study was to explore the possible associations of the gene polymorphisms (LPL HindIII, LPL Ser447-Ter and APOC3 SstI), diabetes mellitus, and plasma lipids with myocardial infarction. The polymorphisms were assessed by restriction assay in 200 Egyptian MI patients (100 diabetic and 100 non-diabetic) and 100 healthy controls. This study demonstrated that individuals with the H2H2 genotype or S2 allele have more than three times higher relative risk of suffering from MI than those carrying the H1H1 or S1S1. Type 2 DM mainly lowers HDL-C levels in MI patients who carry H2H2 or S2S2 genotype and increases TC, TG, and LDL levels in MI patients carrying H2H2 or S2S2 genotype compared with non-diabetic MI patients carrying the same genotypes. In S447X polymorphism, it was observed that DM led to loss of the protective lipid profile in MI patients carrying 447XX genotype. These findings suggest that H2H2 or S2S2 genotypes are associated with dyslipidemia and increased risk of myocardial infarction. The S447X polymorphism is associated with a favorable lipid profile. However, the association of diabetes mellitus with these polymorphisms leads to unfavorable lipid profile.

Human C-reactive protein gene polymorphism and metabolic syndrome are associated with premature coronary artery disease

The aim of this study was to investigate the association between C-reactive protein (CRP) gene polymorphism and metabolic syndrome (MetS) with premature coronary artery disease (PCAD). 116 patients with PCAD (58 with MetS and 58 without MetS) and 119 controls were included in the study. CRP gene +1059 G>C polymorphism was analyzed by polymerase chain reaction. Serum hs-CRP was measured using high-sensitivity enzyme-linked immunosorbent assay. Carriers of C allele of the CRP +1059 G>C polymorphism had 3.37 fold increased risk to develop MetS in patients with PCAD. In addition CRP gene and hs-CRP levels were independent risk factors for PCAD and MetS. The present study provides new evidence that the presence of CRP +1059 G>C polymorphism and hs-CRP levels are independent determinants of PCAD and MetS in Egyptians. The results of our study suggest a synergistic effect of CRP C allele with classical risk factors such as hypertension, obesity, dyslipidemia and MetS.

Matrix metalloproteinase -9 polymorphism and outcome after acute myocardial infarction.

OBJECTIVES Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of coronary artery disease (CAD). This study aims to determine the association of MMP-9 genotype polymorphisms and its serum levels with the risk of acute myocardial infarction (AMI) in Egyptian patients. Also, it evaluated their role as predictors of AMI outcome after six months follow-up. METHODS Subjects included in the study were 184 patients with AMI and 180 controls. Genotyping of MMP-9-1562C>T polymorphism was carried out by PCR-based restriction digestion method. Serum MMP-9 was measured using ELIZA assay. All patients were followed for AMI complications during their hospitalization and 6 months later on. RESULTS MMP-9-1562T allele was more frequent in patients than in controls (OR=1.65, 95%CI 1.09-2.15, P=0.011). the frequency of CT+TT genotypes were higher in patients with morbidity (OR=2.85, 95%CI 1.29-6.29, P=0.008) and with mortality (OR=3.21, 95%CI 1.28-8.02, P=0.012) than in those without MI complications. Serum MMP-9 levels were significantly elevated in AMI as compared to controls and more associated with TT genotype. The impairment of LV function (ΔEF, ΔLAD, ΔE/A) was more observed in the TT genotype compared with CC genotype. CONCLUSIONS Our data suggest that MMP-9 (TT genotype) and its serum level are associated with the risk of suffering AMI in Egyptians. In addition, MMP-9 polymorphism and its level might be useful clinical biomarkers for predicting the outcome of AMI.

Influence of MTHFR C677T gene polymorphism in the development of cardiovascular disease in Egyptian patients with rheumatoid arthritis

OBJECTIVE To investigate the association between increased carotid intima-media thickness (CIMT), homocysteine level, and MTHFR C677T (rs1801133) gene polymorphism in Egyptian people with rheumatoid arthritis (RA). SUBJECTS AND METHODS 280 Egyptian women (160 RA patients and 120 controls) were included in the study. CIMT was measured using high resolution B-mode ultrasonography and homocysteine levels were measured using enzyme-linked immunosorbent assay. While, MTHFR C677T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS We found that subjects who carried the TT genotype and T allele were significantly more likely to develop RA with 2.9 and 1.5 fold, respectively. RA patients carrying the T allele presented a statistically significant increased risk of developing atherosclerosis compared with those carrying the C allele. Moreover, MTHFR TT genotype was independent risk factor of thick CIMT. CONCLUSIONS C677T MTHFR gene polymorphism is associated with RA in Egyptians. MTHFR 677TT carriers had higher concentrations of serum Hcy than did subjects harboring the CC and CT genotypes. The presence of 677T allele increases the risk of atherosclerosis in patients with RA. This increased risk of atherosclerosis could be due to hyperhomocysteinemia.

Matrix Metalloproteinase 3 Gene Polymorphism and Its Level Predict Morbidity After Acute Myocardial Infarction.

OBJECTIVES Matrix metalloproteinase is responsible for ventricular remodeling after acute myocardial infarction (MI). The purpose of the present study was to determine whether the matrix metalloproteinase 3 (MMP-3) polymorphism and its level predict morbidity after acute MI (AMI). METHODS We studied 112 patients with AMI and 140 controls. All patients were followed for AMI complications during their hospitalization and 6 months after. Serum MMP-3 was measured. MMP-3-1612 5A/6A polymorphism was genotyped by polymerase chain reaction. RESULTS We observed that the serum MMP-3 levels were significantly increased in patients with AMI with morbidity compared with patients without complications. Also, MMP-3 levels in patients with AMI carrying 5A/5A were elevated compared with those carrying 6A/6A. The frequencies of 5A/5A genotypes were significantly increased in patients with AMI compared with controls, and patients with AMI carrying 5A/5A had a fivefold increased risk of developing morbidity. The impairment of left ventricular function (ΔFS [fractional shortening] and ΔEF [ejection fraction]) was observed more in the 5A/5A genotype compared with the 6A/6A genotype. A significant inverse correlation between predischarge MMP-3 levels and FS and EF was found at 6 months follow-up. CONCLUSIONS MMP-3 polymorphism has a significant association with the risk of developing morbidity after AMI. Higher predischarge MMP-3 levels are associated with left ventricular dysfunction after AMI.

A-Wave Acceleration: A New Doppler Echocardiographic Index for Evaluation of Left Ventricular Diastolic Dysfunction in Elderly Patients

Age alters Doppler indexes of left ventricular diastolic performance. Thus, the Doppler detection of left ventricular diastolic dysfunction in the elderly is difficult. The reliability of Doppler indexes in detecting left ventricular diastolic dysfunction in the elderly patients with cardiac diseases known to affect diastolic function were evaluated. Diastolic function using pulsed Doppler in 6 groups of 10 subjects each: elderly normal, young normal, and elderly with hypertrophic cardiomyopathy, aortic stenosis, coronary artery disease, and dilated cardiomyopathy was tested. The comparison of elderly normal with young normal showed that A-wave acceleration did not change significantly. Comparing elderly normal to elderly with diseases showed that all tested indexes except A-wave acceleration failed to separate normal elderly from diseased elderly. A-wave acceleration appears to be a useful index that can help in diagnosis of left ventricular diastolic dysfunction in elderly patients independent of age effects.Age alters Doppler indexes of left ventricular diastolic performance. Thus, the Doppler detection of left ventricular diastolic dysfunction in the elderly is difficult. The reliability of Doppler indexes in detecting left ventricular diastolic dysfunction in the elderly patients with cardiac diseases known to affect diastolic function were evaluated. Diastolic function using pulsed Doppler in 6 groups of 10 subjects each: elderly normal, young normal, and elderly with hypertrophic cardiomyopathy, aortic stenosis, coronary artery disease, and dilated cardiomyopathy was tested. The comparison of elderly normal with young normal showed that A-wave acceleration did not change significantly. Comparing elderly normal to elderly with diseases showed that all tested indexes except A-wave acceleration failed to separate normal elderly from diseased elderly. A-wave acceleration appears to be a useful index that can help in diagnosis of left ventricular diastolic dysfunction in elderly patients independent of age effects.