Maisa Mahmoud | Dasman Diabetes Institute (original) (raw)

Papers by Maisa Mahmoud

Research paper thumbnail of Vitamin D Insufficiency in Arabs and South Asians Positively Associates with Polymorphisms in GC and CYP2R1 Genes

PLoS ONE, 2014

Background: A number of genetic studies have reported an association between vitamin D related ge... more Background: A number of genetic studies have reported an association between vitamin D related genes such as groupspecific component gene (GC), Cytochrome P450, family 2, subfamily R, polypeptide 1 (CYP2R1) and 7-dehydrocholesterol reductase/nicotinamide-adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) and serum levels of the active form of Vitamin D, 25 (OH) D among African Americans, Caucasians, and Chinese. Little is known about how genetic variations associate with, or contribute to, 25(OH)D levels in Arabs populations.

Research paper thumbnail of Vitamin D Insufficiency in Arabs and South Asians Positively Associates with Polymorphisms in GC and CYP2R1 Genes

Background A number of genetic studies have reported an association between vitamin D related ge... more Background

A number of genetic studies have reported an association between vitamin D related genes such as group-specific component gene (GC), Cytochrome P450, family 2, subfamily R, polypeptide 1 (CYP2R1) and 7-dehydrocholesterol reductase/nicotinamide-adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) and serum levels of the active form of Vitamin D, 25 (OH) D among African Americans, Caucasians, and Chinese. Little is known about how genetic variations associate with, or contribute to, 25(OH)D levels in Arabs populations.

Methods

Allele frequencies of 18 SNPs derived from CYP2R1, GC, and DHCR7/NADSYN1 genes in 1549 individuals (Arabs, South Asians, and Southeast Asians living in Kuwait) were determined using real time genotyping assays. Serum levels of 25(OH)D were measured using chemiluminescence immunoassay.

Results

GC gene polymorphisms (rs17467825, rs3755967, rs2282679, rs7041 and rs2298850) were found to be associated with 25(OH)D serum levels in Arabs and South Asians. Two of the CYP2R1 SNPs (rs10500804 and rs12794714) and one of GC SNPs (rs1155563) were found to be significantly associated with 25(OH)D serum levels only in people of Arab origin. Across all three ethnicities none of the SNPs of DHCR7/NADSYN1 were associated with serum 25(OH)D levels and none of the 18 SNPs were significantly associated with serum 25(OH)D levels in people from South East Asia.

Conclusion

Our data show for the first time significant association between the GC (rs2282679 and rs7041), CYP2R1 (rs10741657) SNPs and 25(OH)D levels. This supports their roles in vitamin D Insufficiency in Arab and South Asian populations respectively. Interestingly, two of the CYP2R1 SNPs (rs10500804 and rs12794714) and one GC SNP (rs1155563) were found to correlate with vitamin D in Arab population exclusively signifying their importance in this population.

Research paper thumbnail of Insight into the impact of diabetes mellitus on the increased risk of hepatocellular carcinoma: mini-review

Hepatocellular carcinoma is a multifactorial disease which is associated with a background of man... more Hepatocellular carcinoma is a multifactorial disease which is associated with a background of many causal risk factors. Diabetes mellitus however is one of the most common co-morbid illnesses found in hepatocellular carcinoma patients that are significantly associated with worsening of hepatocellular carcinoma development, patient prognosis and survival. Therefore, efforts have been focused on understanding the mechanisms underlying progression of hepatocellular carcinoma onset and development especially in diabetic patients. To our knowledge, there are no reports which address the impact of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) along with epigenetic regulations associated with increased risk of hepatocellular carcinoma confounded by diabetes mellitus. Therefore,
this mini-review focuses on the possible intermediary mechanisms involved in worsening the onset and progression of hepatocellular carcinoma development confounded by diabetes mellitus. The first approach is to look at the role of inflammatory mediators (TNF-α and IL-6) in apoptosis and inflammation during hepatocarcinogenesis through monitoring levels of apoptotic regulators, B-cell lymphoma 2 protein which is encoded by BCL2 gene and apoptosis regulator BAX known as bcl-2-like protein 4 which is encoded by the BAX gene. The second approach is to focus on the possible epigenomic reprogramming that drives hepatocellular transformation since epigenetic modification of DNA is a key feature in the pathogenesis of hepatocarcinogenesis. Both approaches may suggest role of using Bcl2 and Bax as apoptotic and inflammatory markers for hepatocellular carcinoma detection as well as the importance impact of DNA methylation, hypomethylation or histone modifications as attractive candidates for early-detection biomarkers of hepatocellular carcinoma.
Keywords: Apoptosis and inflammation, Diabetes mellitus, DNA methylation or histone modifications, Epigenomic reprogramming, Hepatocarcinogenesis, Hepatocellular carcinoma

Research paper thumbnail of Comparative evaluation of iNNO-LIPA HBV assay, direct DNA sequencing and subtractive PCR-RFLP for genotyping of clinical HBV isolates

Genotypes (A to H) of hepatitis B virus (HBV) influence liver disease progression and response to... more Genotypes (A to H) of hepatitis B virus (HBV) influence liver disease progression and response to antiviral therapy in HBV-infected patients. Several methods have been developed for rapid genotyping of HBV strains. However, some of these methods may not be suitable for developing countries. The performance of INNO-LiPA HBV Genotyping assay (LiPA), direct DNA sequencing and subtractive PCR-RFLP of genotype-specific HBV genome regions were evaluated for accurately determining the HBV genotypes by analyzing sera (n = 80) samples from chronic HBV patients. Both, LiPA and DNA sequencing identified 63, 4 and 13 HBV strains as belonging to genotype D, genotype A and mixed genotype A and D, respectively. On the contrary, the PCR-RFLP-based method correctly identified all 4 genotype A but only 56 of 63 genotype D strains. Seven genotype D strains yielded indeterminate results. DNA sequence comparisons showed that a single nucleotide change in the target region generated an additional restriction site for Nla IV that compromised the accuracy of this method. Furthermore, all the mixed genotype A and D strains were identified only as genotype A strains. The data show that the PCR-RFLP-based method incorrectly identified some genotype D strains and failed to identify mixed genotype infections while LiPA and DNA sequencing yielded accurate results.

Research paper thumbnail of Mutation Patterns at Codons Rt204 And Rt180 of the HBV Polymerase Gene Associated with Lamivudine Resistance in Treated and Untreated Chronic HBV Patients in Kuwait: A Case Series

Given the loss of therapeutic efficacy associated with the development of resistance to lamivudin... more Given the loss of therapeutic efficacy associated with the development of resistance to lamivudine and the availability of new Abstract Introduction: Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication via suppression of the RNAdependent DNA polymerase. However, patients with prolonged therapy were previously detected harboring drugresistant mutants. Such mutants though partially replication defective, confer resistance to lamivudine and can elicit exacerbation of hepatonecro-inflammation.

Research paper thumbnail of Construction of a modified vector for efficient purification of recombinant Mycobacterium tuberculosis proteins expressed in Escherichia coli

A major problem in assessing the vaccine and diagnostic potential of various proteins encoded by ... more A major problem in assessing the vaccine and diagnostic potential of various proteins encoded by Mycobacterium tuberculosis genome is the inability to produce large quantities of these proteins, even when Escherichia coli or other heterologous systems are employed for recombinant protein production. To overcome these barriers, we have constructed a modified expression vector, using pGEX-4T-1 vector as the backbone. In addition to the features offered by the pGEX-4T vectors, the new vector allowed easy purification of recombinant proteins on the highly versatile Ni-NTA-agarose affinity matrix. The utility of the new vector was demonstrated by expressing and purifying, to near homogeneity, two M. tuberculosis proteins, i.e., Rv3872 (a member of the multigene PE subfamily) and Rv3873 (a member of the multi-gene PPE subfamily), which are encoded by the RD1 region of M. tuberculosis. The proteins encoded by rv3872 and rv3873 were expressed at high levels as fusion proteins with glutathione-S-transferase in E. coli. The recombinant Rv3872 and Rv3873 proteins were purified and isolated free of the fusion partner (GST) by affinity purification on glutathione-Sepharose and/or Ni-NTA-agarose affinity matrix and cleavage of the purified fusion proteins by thrombin protease. The recombinant Rv3872 protein was nearly homogeneous (more than 95% pure) while Rv3873 preparation was more than 90% pure. The recombinant Rv3872 and Rv3873 proteins were immunologically active and reacted with antibodies in sera from TB patients. Our results demonstrate the utility of the newly constructed expression vector with two affinity tags for efficient expression and purification of recombinant M. tuberculosis proteins expressed in E. coli, which could be used for further diagnostic and immunological studies.

Research paper thumbnail of Sudden cardiac death diagnosed with dilated cardiomyopathy in a Kuwaiti family: a case report

BMC research notes, 2014

Dilated cardiomyopathy is myocardial disease characterized by dilatation and impaired contraction... more Dilated cardiomyopathy is myocardial disease characterized by dilatation and impaired contraction of the left ventricle or both left and right ventricle. The majority of these cases are secondary to coronary artery disease, hypertension and valvular cardiomyopathy. Patients diagnosed with dilated cardiomyopathy are further clinically evaluated for evidence of familial history of the disease. Those families have shown to have genetic predisposition to dilated cardiomyopathy; thus, currently there is no available single genetic test that allows comprehensive testing of all causative genes. We report a Kuwaiti case of dilated cardiomyopathy that was diagnosed at young age. The patient clinical presentation pointed out to the fact that this was a familial disease. This case is the first reported in Kuwait clinically presented with familial dilated cardiomyopathy implying a genetic susceptibility factor to be further investigated within the at-risk family members. 23-year-old Arab ethnic...

Research paper thumbnail of Vitamin D Insufficiency in Arabs and South Asians Positively Associates with Polymorphisms in GC and CYP2R1 Genes

PLoS ONE, 2014

Background: A number of genetic studies have reported an association between vitamin D related ge... more Background: A number of genetic studies have reported an association between vitamin D related genes such as groupspecific component gene (GC), Cytochrome P450, family 2, subfamily R, polypeptide 1 (CYP2R1) and 7-dehydrocholesterol reductase/nicotinamide-adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) and serum levels of the active form of Vitamin D, 25 (OH) D among African Americans, Caucasians, and Chinese. Little is known about how genetic variations associate with, or contribute to, 25(OH)D levels in Arabs populations.

Research paper thumbnail of Vitamin D Insufficiency in Arabs and South Asians Positively Associates with Polymorphisms in GC and CYP2R1 Genes

Background A number of genetic studies have reported an association between vitamin D related ge... more Background

A number of genetic studies have reported an association between vitamin D related genes such as group-specific component gene (GC), Cytochrome P450, family 2, subfamily R, polypeptide 1 (CYP2R1) and 7-dehydrocholesterol reductase/nicotinamide-adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) and serum levels of the active form of Vitamin D, 25 (OH) D among African Americans, Caucasians, and Chinese. Little is known about how genetic variations associate with, or contribute to, 25(OH)D levels in Arabs populations.

Methods

Allele frequencies of 18 SNPs derived from CYP2R1, GC, and DHCR7/NADSYN1 genes in 1549 individuals (Arabs, South Asians, and Southeast Asians living in Kuwait) were determined using real time genotyping assays. Serum levels of 25(OH)D were measured using chemiluminescence immunoassay.

Results

GC gene polymorphisms (rs17467825, rs3755967, rs2282679, rs7041 and rs2298850) were found to be associated with 25(OH)D serum levels in Arabs and South Asians. Two of the CYP2R1 SNPs (rs10500804 and rs12794714) and one of GC SNPs (rs1155563) were found to be significantly associated with 25(OH)D serum levels only in people of Arab origin. Across all three ethnicities none of the SNPs of DHCR7/NADSYN1 were associated with serum 25(OH)D levels and none of the 18 SNPs were significantly associated with serum 25(OH)D levels in people from South East Asia.

Conclusion

Our data show for the first time significant association between the GC (rs2282679 and rs7041), CYP2R1 (rs10741657) SNPs and 25(OH)D levels. This supports their roles in vitamin D Insufficiency in Arab and South Asian populations respectively. Interestingly, two of the CYP2R1 SNPs (rs10500804 and rs12794714) and one GC SNP (rs1155563) were found to correlate with vitamin D in Arab population exclusively signifying their importance in this population.

Research paper thumbnail of Insight into the impact of diabetes mellitus on the increased risk of hepatocellular carcinoma: mini-review

Hepatocellular carcinoma is a multifactorial disease which is associated with a background of man... more Hepatocellular carcinoma is a multifactorial disease which is associated with a background of many causal risk factors. Diabetes mellitus however is one of the most common co-morbid illnesses found in hepatocellular carcinoma patients that are significantly associated with worsening of hepatocellular carcinoma development, patient prognosis and survival. Therefore, efforts have been focused on understanding the mechanisms underlying progression of hepatocellular carcinoma onset and development especially in diabetic patients. To our knowledge, there are no reports which address the impact of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) along with epigenetic regulations associated with increased risk of hepatocellular carcinoma confounded by diabetes mellitus. Therefore,
this mini-review focuses on the possible intermediary mechanisms involved in worsening the onset and progression of hepatocellular carcinoma development confounded by diabetes mellitus. The first approach is to look at the role of inflammatory mediators (TNF-α and IL-6) in apoptosis and inflammation during hepatocarcinogenesis through monitoring levels of apoptotic regulators, B-cell lymphoma 2 protein which is encoded by BCL2 gene and apoptosis regulator BAX known as bcl-2-like protein 4 which is encoded by the BAX gene. The second approach is to focus on the possible epigenomic reprogramming that drives hepatocellular transformation since epigenetic modification of DNA is a key feature in the pathogenesis of hepatocarcinogenesis. Both approaches may suggest role of using Bcl2 and Bax as apoptotic and inflammatory markers for hepatocellular carcinoma detection as well as the importance impact of DNA methylation, hypomethylation or histone modifications as attractive candidates for early-detection biomarkers of hepatocellular carcinoma.
Keywords: Apoptosis and inflammation, Diabetes mellitus, DNA methylation or histone modifications, Epigenomic reprogramming, Hepatocarcinogenesis, Hepatocellular carcinoma

Research paper thumbnail of Comparative evaluation of iNNO-LIPA HBV assay, direct DNA sequencing and subtractive PCR-RFLP for genotyping of clinical HBV isolates

Genotypes (A to H) of hepatitis B virus (HBV) influence liver disease progression and response to... more Genotypes (A to H) of hepatitis B virus (HBV) influence liver disease progression and response to antiviral therapy in HBV-infected patients. Several methods have been developed for rapid genotyping of HBV strains. However, some of these methods may not be suitable for developing countries. The performance of INNO-LiPA HBV Genotyping assay (LiPA), direct DNA sequencing and subtractive PCR-RFLP of genotype-specific HBV genome regions were evaluated for accurately determining the HBV genotypes by analyzing sera (n = 80) samples from chronic HBV patients. Both, LiPA and DNA sequencing identified 63, 4 and 13 HBV strains as belonging to genotype D, genotype A and mixed genotype A and D, respectively. On the contrary, the PCR-RFLP-based method correctly identified all 4 genotype A but only 56 of 63 genotype D strains. Seven genotype D strains yielded indeterminate results. DNA sequence comparisons showed that a single nucleotide change in the target region generated an additional restriction site for Nla IV that compromised the accuracy of this method. Furthermore, all the mixed genotype A and D strains were identified only as genotype A strains. The data show that the PCR-RFLP-based method incorrectly identified some genotype D strains and failed to identify mixed genotype infections while LiPA and DNA sequencing yielded accurate results.

Research paper thumbnail of Mutation Patterns at Codons Rt204 And Rt180 of the HBV Polymerase Gene Associated with Lamivudine Resistance in Treated and Untreated Chronic HBV Patients in Kuwait: A Case Series

Given the loss of therapeutic efficacy associated with the development of resistance to lamivudin... more Given the loss of therapeutic efficacy associated with the development of resistance to lamivudine and the availability of new Abstract Introduction: Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication via suppression of the RNAdependent DNA polymerase. However, patients with prolonged therapy were previously detected harboring drugresistant mutants. Such mutants though partially replication defective, confer resistance to lamivudine and can elicit exacerbation of hepatonecro-inflammation.

Research paper thumbnail of Construction of a modified vector for efficient purification of recombinant Mycobacterium tuberculosis proteins expressed in Escherichia coli

A major problem in assessing the vaccine and diagnostic potential of various proteins encoded by ... more A major problem in assessing the vaccine and diagnostic potential of various proteins encoded by Mycobacterium tuberculosis genome is the inability to produce large quantities of these proteins, even when Escherichia coli or other heterologous systems are employed for recombinant protein production. To overcome these barriers, we have constructed a modified expression vector, using pGEX-4T-1 vector as the backbone. In addition to the features offered by the pGEX-4T vectors, the new vector allowed easy purification of recombinant proteins on the highly versatile Ni-NTA-agarose affinity matrix. The utility of the new vector was demonstrated by expressing and purifying, to near homogeneity, two M. tuberculosis proteins, i.e., Rv3872 (a member of the multigene PE subfamily) and Rv3873 (a member of the multi-gene PPE subfamily), which are encoded by the RD1 region of M. tuberculosis. The proteins encoded by rv3872 and rv3873 were expressed at high levels as fusion proteins with glutathione-S-transferase in E. coli. The recombinant Rv3872 and Rv3873 proteins were purified and isolated free of the fusion partner (GST) by affinity purification on glutathione-Sepharose and/or Ni-NTA-agarose affinity matrix and cleavage of the purified fusion proteins by thrombin protease. The recombinant Rv3872 protein was nearly homogeneous (more than 95% pure) while Rv3873 preparation was more than 90% pure. The recombinant Rv3872 and Rv3873 proteins were immunologically active and reacted with antibodies in sera from TB patients. Our results demonstrate the utility of the newly constructed expression vector with two affinity tags for efficient expression and purification of recombinant M. tuberculosis proteins expressed in E. coli, which could be used for further diagnostic and immunological studies.

Research paper thumbnail of Sudden cardiac death diagnosed with dilated cardiomyopathy in a Kuwaiti family: a case report

BMC research notes, 2014

Dilated cardiomyopathy is myocardial disease characterized by dilatation and impaired contraction... more Dilated cardiomyopathy is myocardial disease characterized by dilatation and impaired contraction of the left ventricle or both left and right ventricle. The majority of these cases are secondary to coronary artery disease, hypertension and valvular cardiomyopathy. Patients diagnosed with dilated cardiomyopathy are further clinically evaluated for evidence of familial history of the disease. Those families have shown to have genetic predisposition to dilated cardiomyopathy; thus, currently there is no available single genetic test that allows comprehensive testing of all causative genes. We report a Kuwaiti case of dilated cardiomyopathy that was diagnosed at young age. The patient clinical presentation pointed out to the fact that this was a familial disease. This case is the first reported in Kuwait clinically presented with familial dilated cardiomyopathy implying a genetic susceptibility factor to be further investigated within the at-risk family members. 23-year-old Arab ethnic...