Browsing by Author "Hassanein S.I."

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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.
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
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.