Abid Azhar

Publications

1 Serum Nitric Oxide and Sialic Acid: Possible Biochemical Markers for Progression of Diabetic Nephropathy

Authors: Syed M. Shahid, Rozeena Shaikh, Syeda N. Nawab, Shah A. Qader, Abid Azhar, Tabassum Mahboob

Abstract:

This study was designed to investigate the role of serum nitric oxide and sialic acid in the development of diabetic nephropathy as disease marker. Total 210 diabetic patients (age and sex matched) were selected followed by informed consent and divided into four groups (70 each) as I: control; II: diabetic; III: diabetic hypertensive; IV: diabetic nephropathy. The blood samples of all subjects were collected and analyzed for serum nitric oxide, sialic acid, fasting blood glucose, serum urea, creatinine, HbA1c and GFR. The BMI, systolic and diastolic blood pressures, blood glucose, HbA1c and serum sialic acid levels were high (p<0.01) in group II as compared to control subjects. The higher levels (p<0.01) of BMI, systolic and diastolic blood pressures, blood glucose, HbA1c, serum urea, creatinine and sialic acid were observed in group III and IV as compared to controls. Significantly low levels of GFR and serum nitric oxide (p<0.01) were observed in group III and IV as compared to controls. Results indicated that serum nitric oxide and sialic acid are the major biochemical indicators for micro and macrovascular complications of diabetes such as hypertension and nephropathy. These should be taken into account during screening procedures regarding identifications of the diabetic patients to get them rid of progressive renal impairment to ESRD.

Keywords: Hypertension, Diabetic Nephropathy, Nitric Oxide, sialic acid

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Abstracts

4 Association of AGT (M268T) Gene Polymorphism in Diabetes and Nephropathy in Pakistan

Authors: Syed M. Shahid, Rozeena Shaikh, Syeda N. Nawab, Abid Azhar

Abstract:

Diabetes mellitus (DM) is a prevalent non-communicable disease worldwide. DM may lead to many vascular complications like hypertension, nephropathy, retinopathy, neuropathy and foot infections. Pathogenesis of diabetic nephropathy (DN) is implicated by the polymorphisms in genes encoding the specific components of renin angiotensin aldosterone system (RAAS) which include angiotensinogen (AGT), angiotensin-II receptor and angiotensin converting enzyme (ACE) genes. This study was designed to explore the possible association of AG (M268T) polymorphism in the patients of diabetes and nephropathy in Pakistan. Study subjects included 100 controls, 260 diabetic patients without renal insufficiency and 190 diabetic nephropathy patients with persistent albuminuria. Fasting blood samples were collected from all the subjects after getting institutional ethical approval and informed consent. The biochemical estimations, PCR amplification and direct sequencing for the specific region of AGT gene was carried out. A significantly high frequency of TT genotype and T allele of AGT (M268T) was observed in the patients of diabetes with nephropathy as compared to controls and diabetic patients without any known renal impairment. The TT genotype and T allele of AGT (M268T) polymorphism may be considered as a genetic risk factor for the development and progression of nephropathy in diabetes. Further cross sectional population studies would be of help to establish and confirm the observed possible association of AGT gene variations with development of nephropathy in diabetes.

Keywords: Diabetes, RAAS, AGT (M268T), nephropathy

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3 Angiotensin Converting Enzyme (ACE) and Angiotensinogen (AGT) Gene Variants in Pakistani Patients of Diabetes Mellitus and Diabetic Nephropathy

Authors: Muhammad Ismail, Rozeena Shaikh, Abid Azhar, Jamil Ahmad, Syed M Shahid, Qaisar Mansoor

Abstract:

Introduction: Diabetes mellitus (DM) is a prevalent non-communicable disease worldwide. In most high-income countries as well as middle-income and low- income countries. DM is among the top causes of deaths. DM may lead to many vascular complications like hypertension, nephropathy, retinopathy, neuropathy, and foot. Diabetic nephropathy (DN) characterized by persistent albuminuria is a leading cause of end stage renal failure (ESRF). Pathogenesis of diabetic nephropathy is implicated by the polymorphisms in genes encoding the components of reninangiotensin- aldosteron system (RAAS) which include angiotensinogen (AGT), angiotensin-II receptor and particularly angiotensin converting enzyme (ACE) gene. Method: Study subjects include 110 control, 110 patients with DM without hypertension, 110 patients with DM with hypertension and 110 patients with DN. Blood samples were collected for Biochemical analysis and PCR and sequencing for the specific region of both genes. Results: The frequency of DD genotype and D allele of ACE (I/D) was significantly (p<0.05) high in DM normotensive, DM hypertensive and DN patients when compared to control. The ACE G2350A genotypes and allele frequencies were significantly different (p<0.05) in DM hypertensive patients as compared to control and DN, while no difference was observed between DM normotensive and DN when compared to control. The genotypes and alleles of AGT (M268T) polymorphism were significantly different (p<0.05) in DM normotensive, DM hypertensive and DN when compared to control. Conclusion: The DD genotype and D allele of ACE (I/D), GG genotype and G allele of ACE (G2350A) and the TT genotype and T allele of AGT (M268T) polymorphism have shown a significant difference in genotype and allele frequencies between controls and patients.

Keywords: Pakistan, diabetes mellitus, Diabetic Nephropathy, Genetic Variations, ACE, AGT

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2 Human TP53 Three Dimentional (3D) Core Domain Hot Spot Mutations at Codon, 36, 72 and 240 are Associated with Oral Squamous Cell Carcinoma

Authors: Abid Azhar, Abdul Hameed, Saima Saleem, Zubair Abbasi, Mansoor Ahmed Khan, Navid Rashid Qureshi

Abstract:

Oral Squamous Cell Carcinoma (OSCC) is the leading cause of death in the developing countries like Pakistan. This problem aggravates because of the excessive use of available chewing products. In spite of widespread information on their use and purported legislations against their use the Pakistani markets are classical examples of selling chewable carcinogenic mutagens. Reported studies indicated that these products are rich in reactive oxygen species (ROS) and polyphenols. TP53 gene is involved in the suppression of tumor. It has been reported that somatic mutations caused by TP53 gene are the foundation of the cancer. This study aims to find the loss of TP53 functions due to mutation/polymorphism caused by genomic alteration and interaction with tobacco and its related ingredients. Total 260 tissues and blood specimens were collected from OSCC patients and compared with age and sex matched controls. Mutations in exons 2-11 of TP53 were examined by PCR-SSCP. Samples showing mobility shift were directly sequenced. Two mutations were found in exon 4 at nucleotide position 108 and 215 and one in exon 7 at nucleotide position 719 of the coding sequences in patient’s tumor samples. These results show that substitution of proline with arginine at codon 72 and serine with threonine at codon 240 of p53 protein. These polymorphic changes, found in tumor samples of OSCC, could be involved in loss of heterozygocity and apoptotic activity in the binding domain of TP53. The model of the mutated TP53 gene elaborated a nonfunctional unfolded p53 protein, suggesting an important role of these mutations in p53 protein inactivation and malfunction. This nonfunctional 3D model also indicates that exogenous tobacco related carcinogens may act as DNA-damaging agents affecting the structure of DNA. The interpretations could be helpful in establishing the pathways responsible for tumor formation in OSCC patients.

Keywords: TP53 mutation/polymorphism, OSCC, PCR-SSCP, direct DNA sequencing

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1 Subfamilial Relationships within Solanaceae as Inferred from atpB-rbcL Intergenic Spacer

Authors: Ishrat Jamil, Syeda Qamarunnisa, Abid Azhar, Zabta K. Shinwari, Syed Irtifaq Ali

Abstract:

A phylogenetic analysis of family Solanaceae was conducted using sequence data from the chloroplast intergenic atpB-rbcL spacer. Sequence data was generated from 17 species representing 09 out of 14 genera of Solanaceae from Pakistan. Cladogram was constructed using maximum parsimony method and results indicate that Solanaceae is mainly divided into two subfamilies; Solanoideae and Cestroideae. Four major clades within Solanoideae represent tribes; Physaleae, Capsiceae, Datureae and Solaneae are supported by high bootstrap value and the relationships among them are not corroborating with the previous studies. The findings established that subfamily Cestroideae comprised of three genera; Cestrum, Lycium, and Nicotiana with high bootstrap support. Position of Nicotiana inferred with atpB-rbcL sequence is congruent with traditional classification, which placed the taxa in Cestroideae. In the current study Lycium unexpectedly nested with Nicotiana with 100% bootstrap support and identified as a member of tribe Nicotianeae. Expanded sampling of other genera from Pakistan could be valuable towards improving our understanding of intrafamilial relationships within Solanaceae.

Keywords: Phylogenetics, systematics, solanaceae, intergenic spacer, tribes

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