Browsing by Author "Gad M.Z."

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AGXT2 and DDAH-1 genetic variants are highly correlated with serum ADMA and SDMA levels and with incidence of coronary artery disease in Egyptians
(Springer Netherlands, 2018) Amir M.; Hassanein S.I.; Abdel Rahman M.F.; Gad M.Z.; Clinical Biochemistry Unit; Faculty of Pharmacy and Biotechnology; German University in Cairo (GUC); Main Entrance El-Tagamoa El-Khames; New Cairo City; Cairo; Egypt; Biochemistry Department; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Cairo; Egypt
Dimethylarginine aminodehydrolase (DDAH1) and alanine glyoxylate aminotransferase2 (AGXT2) are two enzymes that contribute in asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) metabolism. Hence they affect production and bioavailability of eNOS-derived nitric oxide (NO) and consequently healthy blood vessels. The major aims of the current study were to investigate the association of genetic variants of AGXT2 rs37369, AGXT2 rs16899974 and DDAH1 rs997251 SNPs with incidence of coronary artery disease (CAD) in Egyptians and to correlate these variants with the serum levels of ADMA and SDMA. The study included 150 subjects; 100 CAD patients and 50 healthy controls. Genotyping was performed by qPCR while the ADMA and SDMA concentrations were assayed by ELISA. Both serum ADMA and SDMA concentrations were significantly higher in CAD patients compared to controls (both p < 0.0001). Genotype distributions for all studied SNPs were significantly different between CAD patients and controls. Carriers of AGXT2 rs37369-T allele (CT + TT genotypes) and AGXT2 rs16899974-A allele (CA + AA genotypes) had 2.4- and 2.08-fold higher risk of having CAD than CC genotype in both SNPs (p = 0.0050 and 0.0192, respectively). DDAH1 rs997251 TC + CC genotypes were associated with 2.3-fold higher risk of CAD than TT genotype (p = 0.0063). Moreover, the AGXT2 rs37369 TT and AGXT2 rs16899974 AA genotypes were associated with the highest serum ADMA and SDMA while DDAH1 rs997251 CC genotype was associated with the highest ADMA. AGXT2 rs37369-T, AGXT2 rs16899974-A, and DDAH1 rs997251-C alleles represent independent risk factors for CAD in the Egyptians. � 2018, Springer Nature B.V.
Assessment of the link between endothelin K198n Snp, endothelin concentration and acute myocardial infarction in Egyptians
(Blackwell Publishing, 2017) Abdel Rahman M.F.; Hashad I.M.; Abou-Aisha K.; Abdel Maksoud S.M.; Gad M.Z.; Biochemistry Department; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Cairo; Egypt; Clinical Biochemistry Unit; Faculty of Pharmacy & Biotechnology; German University in Cairo; Cairo; Egypt
The aim of the current study was to assess the link between EDN K198N SNP, ET-1 serum concentration and acute myocardial infarction (AMI) in Egyptians. The study cohort consisted of 84 patients at AMI onset and 84 age-matched healthy controls. Endothelin genotypes and concentrations were determined by sequencing and ELISA, respectively. Genotype distribution was not significantly different between AMI patients and controls (P=.8341). The mean serum ET-1 concentration of patients (13.83�0.7�pg/mL) was significantly higher than controls (7.26�0.2�pg/mL) (P<.0001). ET-1 serum concentrations did not vary significantly among various EDN genotypes in patients (P=.378) and controls (P=.6164). Hence, we conclude that EDN K198N genotypes were not related to either ET-1 concentration or incidence of early-onset AMI in Egyptians. But, AMI patients had higher ET-1 concentrations than controls. � 2016 John Wiley & Sons Australia, Ltd
The association of megalin and cubilin genetic variants with serum levels of 25-hydroxvitamin D and the incidence of acute coronary syndrome in Egyptians: A case control study
(Elsevier B.V., 2020) Elsabbagh R.A.; Abdel Rahman M.F.; Hassanein S.I.; Hanafi R.S.; Assal R.A.; Shaban G.M.; Gad M.Z.; Clinical Biochemistry Unit; Faculty of Pharmacy and Biotechnology; The German University in Cairo; Egypt; Biochemistry Department; Faculty of Pharmacy; October University for Modern Science and Arts; 6th of October City; Egypt; Department of Pharmaceutical Chemistry; Faculty of Pharmacy and Biotechnology; The German University in Cairo; Egypt; Department of Pharmacology and Toxicology; Faculty of Pharmacy and Biotechnology; The German University in Cairo; Egypt; National Heart Institute; Cairo; Egypt
Megalin and cubilin are two receptors that mediate endocytosis of 25-hydroxyvitamin D (25(OH)D) for its final activation by hydroxylation. The aim of the present study was to evaluate the association of polymorphisms in megalin (rs2075252 and rs4668123) and cubilin (rs1801222 and rs12766939) with the circulating serum levels of 25(OH)D and with the early incidence of acute coronary syndrome (ACS) in Egyptians. The study included 328 subjects; 185 ACS patients aged between 27 and 60 years, and 143 healthy age-matched controls. Genotyping of cubilin rs12766939 Single Nucleotide Polymorphism (SNP) was performed using Real-Time Polymerase Chain Reaction (qPCR) and for megalin rs4668123 and rs2075252 and cubilin rs1801222 by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP). 25(OH)D levels were measured by Ultra Performance Liquid Chromatography- Tandem Mass Spectroscopy (UPLC-MS/MS). Results showed that vitamin D deficiency was highly linked to ACS incidence (P < 0.0001). The megalin rs4668123 CC, cubilin rs1801222 GG and cubilin rs12766939 GG + GA genotypes are associated with a higher ACS incidence and can be considered risk factors, according to Chi-squared test (P = 0.0003, 0.0442, 0.013 respectively). Conversely, the megalin rs2075252 SNP was not associated with increased ACS incidence. However, after performing multiple logistic regression analysis, only the megalin rs4668123 SNP was considered an independent ACS risk factor. Furthermore, the megalin rs4668123 CC genotype was associated with lower 25(OH)D levels (P = 0.0018). In conclusion, megalin rs4668123 (CC) was linked to lower 25(OH)D levels and can be considered an independent risk factor for incidence of ACS. � 2019
C(-260)T polymorphism in CD14 receptor gene of Egyptians with acute myocardial infarction
(Bentham Science Publishers B.V., 2018) Hashad I.M.; Hossni N.M.; Abdel Rahman M.F.; Shehata M.; Shaban G.; Gad M.Z.; Clinical Biochemistry Unit; Faculty of Pharmacy and Biotechnology; The German University in Cairo; Cairo; Egypt; Biochemistry Department; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Cairo; Egypt; Department of Cardiology; Faculty of Medicine; Ain Shams University; Cairo; Egypt; Department of Cardiology; National Heart Institute; Cairo; Egypt
Background: Despite the significance of the traditional risk factors, recently published studies have suggested that inflammatory processes and variations in the genetics of the inflammatory system may participate in the initiation of atherosclerosis and its complications. Objective: To investigate the possible association between CD14 C(-260)T (rs2569190) gene polymorphism and the risk of acute myocardial infarction in the Egyptian population. Methods: We enrolled 100 acute myocardial infarction patients in addition to 107 healthy controls. Deoxyribonucleic acid was extracted, purified and used for the genotype assay of C(-260)T polymorphism in promoter region of CD14 gene. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism. Polymerase chain reaction product was digested using a restriction enzyme and the digestion products were specified. Serum CD14 levels were determined by Enzyme Linked Immunosorbent Assay. Results: CD14 genotypic distribution (CC: 15.9% vs. 16%, CT: 62.6% vs. 58%, TT: 21.5% vs. 26% in controls versus acute myocardial infarction patients, p > 0.05 for all variables) and allele frequencies (C allele: 47% vs., 45%, T allele: 52% vs. 55% in controls versus acute myocardial infarction patients, p > 0.05 for all variables) did not show a statistical significant difference. Serum CD14 levels were elevated in acute myocardial infarction patients (5.73�0.62 vs. 4.48�0.28 pg/ml, p < 0.05). However, there was no statistically significant difference in serum CD14 levels among different CD14 genotypes. Conclusion: CD14 C-(260)T polymorphism is not associated with incidence of acute myocardial infarction in Egyptians who showed elevated serum CD14 levels in comparison to healthy individuals. � 2018 Bentham Science Publishers.
Contribution of cyp27b1 and cyp24a1 genetic variations to the incidence of acute coronary syndrome and to vitamin d serum level
(Canadian Science Publishing, 2019) Fam M.S.; Hassanein S.I.; Rahman M.F.A.; Assal R.A.; Hanafi R.S.; Gad M.Z.; Clinical Biochemistry Unit; Faculty of Pharmacy and Biotechnology; German University in Cairo; Fifth Settlement; Cairo; 11432; Egypt; Biochemistry Department; Faculty of Pharmacy; October University for Modern Sciences and Arts; 6th of October; Giza 12566; Egypt; The Molecular Pathology Research Group; Department of Pharmacology and Toxicology; Faculty of Pharmacy and Biotechnology; German University in Cairo; Fifth Settlement; Cairo; 11432; Egypt; Pharmaceutical Chemistry Department; Faculty of Pharmacy and Biotechnology; German University in Cairo; Fifth Settlement; Cairo; 11432; Egypt
Cardiovascular diseases remain a major public health burden worldwide. It was reported that vitamin D protects the cardiovascular system through several mechanisms mainly by hindering atherosclerosis development. Genetic variations in vitamin D metabolic pathway were found to affect vitamin D levels. This study aimed at investigating the association between single nucleotide polymorphisms in genes involved in vitamin D metabolism, CYP27B and CYP24A1; 25-hydroxyvitamin D (25(OH)D) levels; and susceptibility to acute coronary syndrome (ACS). One hundred and eighty-five patients and 138 healthy controls were recruited. CYP24A1 rs2762939 was genotyped using fast real-time PCR, while CYP24A1 rs4809960 and CYP27B1 rs703842 were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism (PCR�RFLP). 25(OH)D3 and 25(OH)D2 levels were measured using ultra-performance liquid chromatography tandem mass spectrum. Vitamin D level was significantly lower in patients than controls (p < 0.05). The GG genotype of rs2762939 was significantly associated with the risk of ACS development, but not correlated to the vitamin D level. rs4809960 and rs703842 genetic variations were not associated with ACS nor with 25(OH)D level. The genetic variant rs2762939 of CYP24A1 is remarkably associated with ACS. Meanwhile, the variants rs4809960 and rs703842 are not associated with ACS incidence. � 2019, Canadian Science Publishing. All rights reserved.
Genetic variants of CYP2R1 are key regulators of serum vitamin D levels and incidence of myocardial infarction in middle-aged Egyptians
(Bentham Science Publishers B.V., 2018) Sedky N.K.; Rahman M.F.A.; Hassanein S.I.; Gad M.Z.; Clinical Biochemistry Unit; Biochemistry Department; Faculty of Pharmacy and Biotechnology; German University in Cairo; New Cairo City; 11835; Egypt; Zewail City of Science and Technology; Giza; 12566; Egypt; Biochemistry Department; Faculty of Pharmacy; October University for Modern Science and Arts (MSA); 6th of October City; Egypt
Background: Myocardial Infarction (MI) is one of the leading causes of morbidity and mortality in Egypt and worldwide. Vitamin D deficiency has long been linked to incidence of cardiovascular diseases. Several factors were reported to contribute to serum vitamin D level including exposure to sunlight. However, genetic variations in the vitamin D metabolic pathways have also been considered as strong determinants of vitamin D levels. CYP2R1 is the major 25-hydroxylase enzyme that is responsible for the 1st activation step of vitamin D. Objective: to investigate the contribution of polymorphisms in CYP2R1 gene to vitamin D deficiency and incidence of MI in Egyptians. Methods: The study included 323 subjects; 185 MI patients and 138 healthy controls. Serum 25OHD3, 25OHD2 and total 25OHD levels were measured using LC-MS/MS. SNPs rs2060793 and rs1993116 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) which is considered one of the most commonly used techniques in genotyping. SNP rs10766197 was detected using TaqMan allele discrimination assay. Results: Serum 25OHD3, 25OHD2 and total 25OHD levels were found to be significantly lower in MI patients than controls. The three studied SNPs were associated with significantly different total 25OHD levels and their genotype distributions differed significantly between MI patients and controls where the high risk genotypes were AG/AA for rs2060793, AG/GG for rs1993116 and AG/AA for rs10766197. Additionally, the concurrent presence of high risk genotypes of the three studied SNPs rendered those individuals at extremely higher risk for MI than each individual SNP (OR 14.1, 95% CI (3.1-64.7), p-value = < 0.0001). Conclusions: Genetic variants of CYP2R1 are key determinants of serum 25OHD levels and are highly associated with MI risk. � 2018 Bentham Science Publishers.
Investigating the link between MCP-1 A-2518G, RANTES G-403A, CX3CR1 V249I and MTHFR C677T gene polymorphisms and the risk of acute myocardial infarction among Egyptians
(Elsevier B.V., 2017) Hashad I.M.; Abdel Rahman M.F.; Alenina N.; Bader M.; Gad M.Z.; Clinical Biochemistry Unit; Faculty of Pharmacy and Biotechnology; German University in Cairo (GUC); New Cairo City; Egypt; Biochemistry Department; Faculty of Pharmacy; October University for Modern Science and Arts (MSA); 6th of October City; Egypt; Cardiovascular Department; Max-Delbr�ck-Center for Molecular Medicine; Berlin-Buch; Germany
Background Acute myocardial infarction (AMI) is one of the leading causes of death among Egyptians. Monocyte chemoattractant protein-1 (MCP-1), regulation on activation normal T cell expressed and secreted (RANTES) and fractalkine (FKN) are chemokines that act as components of inflammatory response while methylenetetrahydrofolate reductase (MTHFR) is important enzyme in folate metabolism essential for homocysteine metabolism. Hyperhomocysteinemia has been linked to AMI. MCP-1 A-2518G, RANTES G-403A, CX3CR1 V249I and MTHFR C677T are important polymorphisms identified in MCP-1, RANTES, CX3CR1 and MTHFR genes respectively. There are conflicting data in the literature about their association with AMI. Therefore, the aim of the current study was to investigate the contribution of these gene variants to risk of AMI among Egyptians. Subjects and methods The study comprised 200 subjects; 100 AMI patients and 100 age-matched healthy controls. The MCP-1, RANTES, CX3CR1 and MTHFR genotypes were determined by restriction fragment length polymorphism (PCR-RFLP). Results Genotypes distributions for RANTES, fractalkine and MTHFR genes were significantly different between AMI patients and controls (p�=�0.0221, 0.0498 and 0.0083) while those results in MCP-1 were not significantly different. A significant risk for AMI with concurrent presence of RANTES (AG/AA), fractalkine (VV) and MTHFR (CT/TT) genotypes was observed. Conclusions 1 - Each of MTHFR 677T, RANTES-403A and CX3CR1 249V alleles is considered an independent risk factor for AMI. 2 - Concurrent presence of high risk genotypes of RANTES (AG/AA), fractalkine (VV) and MTHFR (CT/TT) increases risk of AMI more than their individual risks. 3 - MCP-1 polymorphism is not associated with AMI among Egyptians. � 2016 Elsevier B.V.
A methoxylated quercetin glycoside harnesses HCC tumor progression in a TP53/miR-15/miR-16 dependent manner
(Taylor and Francis Ltd., 2018) Youness R.A.; Assal R.A.; Ezzat Shahira M; Gad M.Z.; Abdel Motaal A.; Department of Pharmaceutical Biology; Faculty of Pharmacy and Biotechnology; German University in Cairo; Cairo; Egypt; Department of Pharmacology and Toxiciology; Faculty of Pharmacy and Biotechnology; German University in Cairo; Cairo; Egypt; Department of Pharmacognosy; Faculty of Pharmacy; Cairo University; Giza; Egypt; Department of Pharmacognosy; Faculty of Pharmacy; Modern Sciences and Arts University; 6th of October; Egypt; Department of Biochemistry; Faculty of Pharmacy and Biotechnology; German University in Cairo; Cairo; Egypt; Department of Pharmacognosy; College of Pharmacy; King Khalid University; Abha; Saudi Arabia
This study focused on studying the impact of flavonoids isolated from Cleome droserifolia on HCC cell lines and to further unveil their possible impact on TP53 and its downstream tumor suppressor miRNAs. Three flavonol glycosides were isolated from C. droserifolia namely, Isorhamnetin-3-O-?-D-glucoside (1), Quercetin-3`-methoxy-3-O-(4``-acetylrhamnoside)-7-O-?-rhamnoside (2), and Kaempferol-4`-methoxy-3,7-O-dirhamnoside (3). They showed a concentration and time dependent reduction in cellular viability and anchorage-independent growth of HCC cells. Moreover, they exhibited a decrease in the migrating capacity of HepG2 cells in a pattern similar to positive control cells. (2) Showed the most potent effects in halting HCC tumorigenic activity (IC50=36 � 1.70 �M) and a repression of the cellular proliferation rate of HepG2 cells. Restoration of TP53 and its downstream tumor suppressor miRNAs; miR-15a, miR-16, miR-34a by (2) was observed. Moreover, attenuation of (2) mediated actions was shown upon using anti-miR-15a and anti-miR-16. To conclude, this study crystallizes a novel role of C. droserifolia in harnessing HCC progression in-vitro with a possible contribution of TP53/miR-15a/miR-16. � 2018, � 2018 Informa UK Limited, trading as Taylor & Francis Group.
Polymorphisms in gap junction proteins and their role in predisposition of acute myocardial infarction in Egyptians
(Bentham Science Publishers B.V., 2017) El Tahry F.A.; Hashad I.M.; Rahman M.F.A.; Gad M.Z.; Clinical Biochemistry Unit; Faculty of Pharmacy and Biotechnology; German University in Cairo; Cairo; Egypt; Biochemistry Department; Faculty of Pharmacy; October University for Modern Science and Arts; 6th of October City; Egypt
Background: Connexin (Cx) proteins are the building blocks of gap junctions. Among these, Cx37 and Cx40 are expressed on vascular system and reported to have cardioprotective role. Linking polymorphisms in genes coding for Cx and coronary artery disease (CAD) risk showed conflicting results in different populations. None has been studied before in Egyptians. Therefore, the aims of this study were to investigate the influence of Cx37 C1019T and Cx40 A71G polymorphisms on the predisposition of acute myocardial infarction (AMI) in Egyptians, to study linkage disequilibrium (LD) and combined effects of single nucleotide polymorphisms (SNPs) and to correlate the genotypes with sVCAM-1 serum levels. Methods: Total of 201 Egyptian subjects were recruited for the study. They were divided into 104 AMI patients and 97 healthy controls. Genotypes for each participant were determined using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum sVCAM-1was measured by ELISA. Results: Allele frequencies for both Cx37 and Cx40 were not significantly different between AMI and Controls (p=0.93 and p=0.26 respectively). Moreover, studying the dominant and recessive models concluded that none of the genotypes was a risk factor. Both SNPs were not in LD (R2=0.0027). Serum analysis showed higher levels of sVCAM-1 in AMI patients (p<0.0001). sVCAM-1 levels were not significantly different among SNPs (Cx37; p=0.244 and Cx40; p=0.266). � 2017 Bentham Science Publishers.
The role of nitric oxide from neurological disease to cancer
(Springer New York LLC, 2017) Maher A.; Abdel Rahman M.F.; Gad M.Z.; Biochemistry Department; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Cairo; Egypt; Clinical Biochemistry Unit; Faculty of Pharmacy & Biotechnology; German University in Cairo (GUC); Cairo; Egypt
Until the beginning of the 1980s, nitric oxide (NO) was just a toxic molecule of a lengthy list of environmental pollutants such as cigarette smoke and smog. In fact, NO had a very bad reputation of being destroyer of ozone, suspected carcinogen and precursor of acid rain. However, by the early 1990s it was well recognized by the medical research community. Over the last two decades, the picture has been totally changed. Diverse lines of evidence have converged to show that this sometime poison is a fundamental player in the everyday business of the human body. NO activity was probed in the brain, arteries, immune system, liver, pancreas, uterus, peripheral nerves, lungs, and almost every system in the human body. NO is a major player in the cardiovascular system as it is involved in regulating blood pressure. In the CNS, it is involved in memory formation and the regulation of cerebral blood flow to ensure adequate supply of blood to the brain. Because NO is involved in many pathways, it has a role in several diseases related to modern life as hypertension, coronary heart diseases, Alzheimer�s Disease, stroke and cancer. This chapter focuses on the discussion of the role of NO in neurological diseases and cancer and how can this Janus-faced molecule play a role in the pathology and personalized treatment of these diseases. � American Association of Pharmaceutical Scientists 2017.