Research: Visiting Associate ProfessorUniversity of California, Irvine · Department of PharmacologyUSA · Irvine
Research: Aleppo UniversityAleppo UniversitySyria · Aleppo
Research: The University of ManchesterThe University of Manchester · Faculty of Life SciencesUnited Kingdom · Manchester
Article: Association between polymorphisms in apoptotic genes and susceptibility for developing breast cancer in Syrian women.[show abstract] [hide abstract]
ABSTRACT: Apoptosis is a major protective mechanism against cancer. The tumor suppressor protein p53 is the central protein in the apoptotic pathway and was shown to harbor mutations in a considerable fraction of breast cancer tumors. The NQO1 was shown to act as a p53 stabilizer and was suggested to play an important role in the protection against carcinogenic catechol estrogens. Functional polymorphisms in TP53 and NQO1 were investigated in relation to breast cancer susceptibility in several studies, primarily involving Asian and Caucasian populations. The aim of the present study was to investigate TP53 and NQO1 polymorphisms and their combined effects with respect to breast cancer susceptibility in a Syrian study cohort. The study cohort consisted of 122 cases and 139 controls. The tetra-primer ARMS-PCR method was used to genotype three TP53 polymorphisms; namely, exon 4 G>C Arg72Pro, IVS3 16 bp Del/Ins, and MspI IVS6+62A>G, and NQO1 C609T (Pro187Ser) polymorphism. Association was tested under six genetic models. We found a significant association for the heterozygous Arg/Pro genotype when combined with heterozygosity for IVS3 16 bp Del/Ins and MspI IVS6+62A>G (OR = 2.05 (1.22-3.47), P = 0.006). No significant association was found for NQO1 C609T or its combinations with TP53 polymorphisms. Our results support an association for TP53 polymorphisms with breast cancer susceptibility in the Syrian population.Breast Cancer Research and Treatment 03/2013; · 4.43 Impact Factor
Article: Allele Frequencies of the Epidermal Growth Factor Receptors Polymorphism R521K in Colorectal Cancer Patients and Healthy Subjects Indicate a Risk-Reducing Effect of K521 in Syrian Population.Ola Haj Mustafa, Abdul Rezzak Hamzeh, Lina Ghabreau, Nizar Akil, Ala-Eddin Almoustafa, Amal Alachkar[show abstract] [hide abstract]
ABSTRACT: Colorectal cancer contributes heavily to cancer morbidity and mortality worldwide. Numerous therapies are currently in use, including monoclonal antibodies against cellular components involved in tumorigenesis such as epidermal growth factor receptors (EGFRs). Studies showed the polymorphism [R521K] GàA in the EGFR gene to be involved in both colorectal cancer susceptibility and clinical response to therapeutics (e.g., Cetuximab). We aimed at uncovering allele frequencies of this polymorphism among Syrian colorectal cancer patients and healthy individuals. Forty-seven patients with colorectal cancer were included in a case-control study along with 48 healthy subjects, all native Syrians. Individuals were genotyped using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) and results were statistically analyzed to elucidate significant differences between the two groups. Allele frequencies were 40.4% (G/G), 57.4% (G/A) and 2.1% (A/A) in colorectal cancer patients and 41.6% (G/G), 43.7% (G/A) and 14.5% (A/A) in healthy subjects. The A/A genotype was significantly lower in colorectal cancer patients than in the control group. Homozygosity for the A allele is linked to reducing the risk of developing colorectal cancer in Syrian patients. The lower prevalence of (A/A) locally may predict sub-optimal rates of clinical response to Cetuximab compared with populations with higher frequencies of the A allele. Larger scale investigations are needed for a stronger conclusion.North American journal of medical sciences. 03/2013; 5(3):202-6.
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ABSTRACT: The tetra-primer ARMS-PCR method offers significant advantages over the commonly used methods to genotype single nucleotide polymorphisms. It offers fast and cost-effective detection and requires minimum level of expertise and basic instrumentation. The benefits of TP-ARMS-PCR increase exponentially upon multiplexing. However, several complications preclude the common use of multiplex TP-ARMS-PCR methods, primarily the lack of robustness and the difficulty of optimization. We have previously developed triplex and quadruplex TP-ARMS-PCR methods involving the simultaneous detection of up to three SNPs in a single reaction and utilized Betaine, a PCR additive used to enable amplification of GC-rich templates with strong secondary structures, in an attempt to facilitate method development and optimization. In the present communication, we introduced experimental data demonstrating the important effects of Betaine on our previous methods and its potential to overcome the ruggedness and robustness issues commonly found in TP-ARMS-PCR methods, and highlighted the general benefits of Betaine with respect to TP-ARMS-PCR. Our data support the routine inclusion of Betaine in all TP-ARMS-PCR methods, especially when multiplexing is concerned.Molecular Biotechnology 02/2013; · 2.17 Impact Factor
Article: Association between Polymorphisms in Genes for Tumor Suppressor Protein p53 and its Regulator NAD(P)H:Quinone Oxidoreductase 1 (NQO1) and Schizophrenia in a Syrian Study Cohort.[show abstract] [hide abstract]
ABSTRACT: BACKGROUND AND AIMS: The contribution of genetic factors to the susceptibility for developing schizophrenia is well established. Several hypotheses have been developed in an attempt to identify the pathophysiological mechanisms in schizophrenia, with several findings implicating an important role for apoptosis. A limited number of studies investigated the effects of polymorphisms in apoptotic genes on the susceptibility to schizophrenia in different ethnic groups, with none involving an Arab population. The aim of the present study was to investigate the association between multiple polymorphisms in genes for the central apoptotic protein p53 and its regulator NQO1 and the susceptibility for developing schizophrenia in an Arab population from Syria. METHODS: The studied polymorphisms included exon 4 G>C Arg72Pro (rs1042522), IVS3 16 bp Del/Ins (rs17878362), and MspI IVS6+62A>G (rs1625895) of the TP53 gene, and C609T of the NQO1 gene. The study cohort consisted of 90 patients and 144 healthy controls. Association with each of the four polymorphisms was tested under numerous genetic models. The four polymorphisms were genotyped simultaneously using a quadruplex Tetra-Primer ARMS-PCR method described earlier. The combined effects of polymorphisms in NQO1 and TP53 genes were examined. RESULTS: No statistically significant association was found for any of the four polymorphisms. CONCLUSIONS: Our results do not support an association between the studied polymorphisms and schizophrenia in the Syrian population.Archives of medical research 01/2013; · 1.88 Impact Factor
Article: Association between MTHFR C677T and A1298C, and MTRR A66G polymorphisms and susceptibility to schizophrenia in a Syrian study cohort.[show abstract] [hide abstract]
ABSTRACT: The folate-homocystiene metabolic pathway has been shown to be involved in the susceptibility for developing schizophrenia by several studies. In the present study we investigated the role of three common polymorphisms of the folate-homocysteine metabolic pathway in an Arab population from Syria consisting of 85 schizophrenic patients and 126 healthy controls. The studied polymorphisms included the MTHFR C677T and A1298C, and MTRR A66G, all of which result into amino acid changes, and were previously shown to yield decreased enzymatic activity and alter plasma homocysteine concentration. While MTHFR C677T and A1298C polymorphisms were not previously studied in an Arab population with respect to the susceptibility for developing schizophrenia, the MTRR A66G was not previously investigated in any population around the world. Our results indicated a strong association between MTHFR A1298C and schizophrenia. The variant C allele frequency was significantly higher in the patients group (40% vs 29.4%, OR=1.6, 95% CI (1.06-2.41), p=0.023). A statistically significant association was found for MTHFR 677TT genotype under the recessive model in the male patients subgroup (OR=2.6, 95% CI (1.04-6.5), p=0.036), and MTHFR 677CT genotype under the overdominant model in the total patients group (OR=0.52 95% CI (0.29-0.92), p=0.024). No statistically significant association was found for MTRR A66G polymorphism on an individual basis. However, a borderline association was found for the CC/GG (C677T/A66G) compound genotype (OR=2.24, 95% CI (0.97-5.15), p=0.053). Our results support the hypothesis of association between schizophrenia and folate-homocystiene metabolic pathway genes.Asian journal of psychiatry. 06/2012; 5(2):144-9.