Fathy, M., M. Kamal, M. Al-Sharkawy, H. Al-Karaksy, and N. Hassan, "Molecular characterization of exons 6, 8 and 9 of ABCB4 gene in children with Progressive Familial Intrahepatic Cholestasis type 3.", Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals, vol. 21, issue 7, pp. 573-7, 2016 Nov. Abstract

AIM OF WORK: To estimate the frequency of mutations involving exons 6, 8 and 9 of Adenosine triphosphate-binding cassette, subfamily B, member 4 (ABCB4) gene among children with progressive intrahepatic cholestasis with high γ-GT activity (PFIC3).

SUBJECTS AND METHODS: Cross sectional study was conducted on 30 children with PFIC3. Genotyping was performed by sequencing analysis of exons 6, 8 and exon 9 of ABCB4 gene.

RESULTS: Heterozygous synonymous polymorphic variant was detected in exon 6 (rs 1202283) and in exon 8 (rs 2109505). No mutations in studied exons were detected.

CONCLUSION: Exons 6, 8 and 9 mutations of ABCB4 gene are not common among Egyptian children with PFIC3.

Fathy, M., M. Kamal, A. Mohy, and A. Nabil, "Impact of CYP3A5 and MDR-1 gene polymorphisms on the dose and level of tacrolimus among living-donor liver transplanted patients: single center experience.", Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals, vol. 21, issue 4, pp. 335-41, 2016. Abstract

AIM OF WORK: To assess the impact of Cytochrome P450 3A5 (CYP3A5) and multidrug resistance-1 gene (MDR-1) single nucleotide polymorphisms on the dose and blood level of tacrolimus among liver transplanted patients.

PATIENTS AND METHODS: We enrolled a prospective study of 41 liver transplanted patients. Dose-adjusted trough blood concentration (C/D ratio) was calculated. Polymerase chain reaction-restriction fragment length polymorphism followed by sequencing was done for genotyping of CYP3A5*3 (6986A > G).

RESULTS: At 1 week, 1 and 3 months C/D ratio were significantly lower in CYP3A5 expressers *1/*1 patients compared to non-expressers *3/*3.

CONCLUSION: CYP3A5 (6986A > G) genotype, rather than MDR-1 (2677G > A/T) variant, has an impact on tacrolimus pharmacokinetics.

Fathy, M., T. Ramzy, M. A. Elmonem, M. Amer, A. Zeidan, F. A. Hassan, and D. A. Mehaney, "Molecular screening of CFTR gene in Egyptian patients with congenital bilateral absence of the vas deferens: a preliminary study.", Andrologia, vol. 48, issue 10, pp. 1307-1312, 2016 Dec. Abstract

In the current study, we enrolled 14 Egyptian infertile males with isolated congenital bilateral absence of the vas deferens (CBAVD). Screening for the most commonly reported 36 CFTR mutations, and the intron 8 (T)n splice variant was performed by multiplex PCR followed by reversed hybridisation. Samples with the 5T variant were picked for DNA sequencing of intron 8/exon 9 region to identify the number of adjacent TG repeats. The p.Phe508del and the p.Ser1251Asn mutations were detected in heterozygous state in three patients (10.7% of alleles) and in one patient (3.6% of alleles), respectively, while the 5T variant was detected in five patients (28.6% of alleles). Among those five patients, four had TG12 repeats and one had TG13 repeats confirming the pathogenic penetrance of all 5T alleles in Egyptian CBAVD patients. The allelic frequencies of the mutations p.Phe508del, p.Ser1251Asn and the 5T variant in 60 Egyptian cystic fibrosis patients were 24.2%, 3.3% and 2.5% respectively. The mutation p.Ser1251Asn was detected for the first time in isolated CBAVD patient in our study. Due to the high prevalence of p.Phe508del mutation and 5T variant in Egyptian CBAVD patients, we recommend their screening initially, ideally followed by full CFTR gene sequencing in unidentified patients.

Kamal, M., M. M. Fathy, E. Taher, M. Hasan, and M. Tolba, "Assessment of the role of paraoxonase gene polymorphism (Q192R) and paraoxonase activity in the susceptibility to atherosclerosis among lead-exposed workers.", Annals of Saudi medicine, vol. 31, issue 5, pp. 481-7, 2011 Sep-Oct. Abstract

BACKGROUND AND OBJECTIVE: Lead exposure is a well known cause of cardiovascular damage, including atherosclerosis. Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus it protects against atherosclerosis. The mechanism by which heavy metals inhibit serum PON1 activity is still not clear. Our aim was to detect the association between lead exposure and serum PON1 activity and lipid profile and also to study the polymorphism of the PON1 gene.

DESIGN AND SETTING: A case-control, cross-sectional study conducted from June 2008 until May 2009.

SUBJECTS AND METHODS: Male workers (n=100) in a lead battery manufactory were recruited for this study. They were compared with 100 male age-matched workers not exposed to lead (control group). Serum lipid profile, paraoxonase activity and lead were measured in blood samples. The DNA was extracted for detecting the Q192R polymorphism of the PON1 gene by polymerase chain reaction followed by restriction fragment length polymorphism.

RESULTS: There was significant difference in triglycerides, total cholesterol and high-density lipoprotein cholesterol (HDL-C) (P=.01, .05 and .04, respectively) between cases and controls. Multiple linear regression analysis showed that blood lead levels were significantly associated with decreased serum paraoxonase activity (P=.03) in lead workers. The paraoxonase genotype QR was the most prevalent in 34/53 subjects (64%) among the lead-exposed groups, while the genotype QQ was more prevalent in the control group, in 15/25 subjects (60%), with a significant difference between the control and other groups (P<.05).

CONCLUSION: Lead exposure is associated with increased triglycerides, total cholesterol and low-density lipoprotein cholesterol and decreased HDL-C. Because of the protective role of PON1 in the development of atherosclerosis, a decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis.

Fathy, M., M. Hamed, O. Youssif, N. Fawzy, and W. Ashour, "Association between environmental tobacco smoke exposure and lung cancer susceptibility: modification by antioxidant enzyme genetic polymorphisms.", Molecular diagnosis & therapy, vol. 18, issue 1, pp. 55-62, 2014 Feb. Abstract

BACKGROUND: Environmental tobacco smoke (ETS) is the primary etiologic factor responsible for lung cancer. However, only 10-15 % of smokers develop lung cancer, suggesting a genetic role in modifying individual susceptibility to lung cancer. Antioxidant enzymes and genetic polymorphisms should be considered.

AIM: The present study aimed to evaluate the role of antioxidant enzyme activity and genetic polymorphisms in modifying the susceptibility to lung cancer among individuals exposed to ETS.

SUBJECTS AND METHODS: A total of 150 male subjects were divided into three groups: 50 lung cancer patients, 50 chronic smokers, and 50 passive smokers. Genotyping of microsomal epoxide hydrolase (mEH) exon 3 (Tyr(113)Hist) and exon 4 (Hist(139)Arg) polymorphisms were done by the polymerase chain reaction-restriction fragment length polymorphism technique. MnSOD (Val(16)Ala) polymorphism was detected by the real time-TaqMan assay. Erythrocyte MnSOD activity was measured spectrophotometrically.

RESULTS: ETS-exposed individuals (both active and passive smokers) who carried the His allele of mEH exon3 have a 2.9-fold increased risk of lung cancer (odds ratio [OR] 2.9, P < 0.001). In addition, ETS-exposed carriers of the Arg allele of mEH exon 4 have a 2.1-fold increased risk of lung cancer (OR 2.1, P = 0.024). However, no association between the MnSOD Val(16)Ala polymorphism and lung cancer was detected among ETS-exposed individuals (OR 1.6, P = 0.147), although the lung cancer group had significantly lower MnSOD activity than the chronic or passive smoker groups (P = 0.03).

CONCLUSIONS: Exons 3 and 4 polymorphisms of the mEH gene may contribute to lung cancer susceptibility through disturbed antioxidant balance. However, this was not the case with the MnSOD Val(16)Ala single-nucleotid polymorphism. Antioxidant enzymes may modulate the influence of ETS exposure on lung cancer risk.

Fathy, M. M., M. E. Abo Taleb, M. S. El Hawary, M. I. Nabih, W. M. Aref, and M. M. Makhlouf, "Assessment of interleukin 28B genotype as a predictor of response to combined therapy with pegylated interferon plus ribavirin in HCV infected Egyptian patients.", Cytokine, vol. 74, issue 2, pp. 268-72, 2015 Aug. Abstract

BACKGROUND AND AIM: Single nucleotide polymorphisms (SNPs) of interleukin 28B (IL28B) gene is associated with spontaneous clearance and variable response to combined therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV) in chronic hepatitis C virus (HCV) infected patients. This study aimed at assessing the value of IL28B rs8099917 gene polymorphism in predicting sustained virological response (SVR) among HCV infected Egyptian patients treated with PEG-IFN and RBV.

METHODS: Our study was conducted on 153 chronic HCV infected patients treated with PEG-IFN and RBV. Genotyping of rs8099917 near the IL-28B gene was performed by Real Time PCR using Taq-Man probe assay.

RESULTS: The overall SVR was achieved in 49.6% of patients. Patients with TT genotype showed significantly higher SVR rate than minor allele (TG/GG) carriers (74% vs. 26%, P=0.004). Logistic regression analysis revealed that TT carriers had 2.8 higher chance for SVR achievement than G allele carriers TG/GG (OR=2.8, 95% CI=1.4-5.6, P=0.004). Younger age, male sex and low activity grading were significant predictors of SVR (P=0.003, P=<0.001 and P<0.001 respectively). High pretreatment AST levels and advanced liver fibrosis were negative predictors of SVR (P=0.04 and P<0.001 respectively).

CONCLUSION: IL28B genotype is a significant pre-treatment predictor of response to PEG-IFN/RBV in HCV infected Egyptian patients.

Nabih, M. I., W. M. Aref, and M. M. Fathy, "Significance of plasma osteopontin in diagnosis of hepatitis C virus-related hepatocellular carcinoma.", Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, vol. 15, issue 3-4, pp. 103-7, 2014 Sep-Dec. Abstract

BACKGROUND AND STUDY AIMS: Alfa fetoprotein (AFP) is widely used as a surveillance test for hepatocellular carcinoma (HCC) among patients with liver cirrhosis (LC). However, the clinical use of AFP has been shown to present some important limitations in sensitivity and specificity. Osteopontin (OPN) is a secreted matrix glycoprotein that is emerging as a significant protein in the biology of HCC. The aim of this study was to assess the diagnostic value of plasma OPN compared with that of AFP in the diagnosis of HCC among hepatitis C virus (HCV)-related LC.

PATIENTS AND METHODS: Plasma levels of OPN and AFP were measured in 69 Egyptian patients with HCV-related LC (35 with HCC and 34 without HCC) and 20 healthy controls.

RESULTS: Both median AFP and OPN levels were significantly higher in the HCC group compared to LC and healthy control groups (p<0.001 in each) and in LC compared to the control group (p<0.001). In the HCC group, both OPN and AFP levels were significantly higher in patients with Child-Pugh class C and B compared to class A (p<0.05 in each). There was no correlation between OPN and AFP levels. The OPN level was significantly higher in patients with multiple focal lesions than in those with single lesions (p<0.05) and in patients with portal vein invasion compared to patients without portal vein invasion (p<0.05). Receiver operator characteristic (ROC) curves showed that the area under the curve (AUC) for OPN and AFP was 0.824 and 0.730, respectively.

CONCLUSION: OPN is a promising tumour marker which could be used as a screening test for the diagnosis of HCC in patients with LC and, hence, improves the prognosis and survival rate of these patients. The association of OPN with the multiplicity of focal lesions and portal vein invasion suggests an additional prognostic value.

Fathy, M. M., N. O. H. A. M. ABDELRAZEK, F. A. Hassan, and A. A. El-Badry, "Molecular copro-prevalence of Cryptosporidium in Egyptian children and evaluation of three diagnostic methods.", Indian pediatrics, vol. 51, issue 9, pp. 727-9, 2014 Sep. Abstract

OBJECTIVE: To determine molecular prevalence of Cryptosporidium in a cohort of Egyptian children and compare three diagnostic tests.

METHODS: Stool samples from children with diarrhea (n=150) and from apparently healthy children (n=100) were examined for Cryptosporidium using microscopy, enzyme linked immuosorbant assay (ELISA) and nested polymerase chain reaction (nPCR).

RESULTS: nPCR detected Cryptosporidium in 22.4% of children. Acid-fast stain and ELISA showed false negativity but 100% specificity with nPCR as gold standard.

CONCLUSION: Cryptosporidium is a common cause of diarrhea in children in Egypt.

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