Taseer Ahmed Khan

Phylogenetic and biological characterization of Newcastle disease virus isolates from Pakistan.

ABSTRACT Eight Newcastle disease virus isolates from Pakistan were sequenced and characterized. A PCR matrix gene assay, designed to detect all avian paramyxovirus 1, did not detect four of the isolates. A new matrix gene test that detected all isolates was developed. Phylogenetic analysis and pathotyping confirmed that virulent viruses of different genotypes are circulating in Pakistan.

New roles of the multidimensional adipokine: chemerin.

The discovery of several adipokines with diverse activities and their involvement in regulation of various pathophysiological functions of human body has challenged the researchers. In the family of adipokine, chemerin is a novel and unique addition. Ever since the first report on chemerin as a chemo-attractant protein, there are numerous studies showing a multitasking capacity of chemerin in the maintenance of homeostasis, for the activation of natural killer cells, macrophages and dendritic cells in both innate and adaptive immunity. Its diversity ranges from generalized inflammatory cascades to being explicitly involved in the manifestation of arthritis, psoriasis and peritonitis. Its association with certain cancerous tissue may render it as a potential tumor marker. In present review, we aim to consolidate recent data of investigations on chemerin in context to functional characteristics with a special reference to its role as a metabolic signal in inflammation and non-metabolic syndromes.

Vitamin D Receptor Cdx-2 Polymorphism and Premenopausal Breast Cancer Risk in Southern Pakistani Patients

Background Vitamin D3 is a secoster oid that exerts its effect by binding to its nuclear receptor called vitamin D receptor (VDR), inducing apoptosis and thereby inhibiting cell proliferation in cancer cells. The VDR receptor, located in the nucleus, is known to regulate the functions of over 200 genes. Various allelic forms of hVDR have been discovered that increase susceptibility to various cancers. The VDR-Cdx2 polymorphism, located in the promoter region of exon 1e in the VDR gene, influences the functional activity of the receptor, since the hVDR lacks consensus TATA and CAAT boxes. The current investigation examines the association between VDR-Cdx2 polymorphism and breast cancer in premenopausal females from Southern Pakistan. Methods We conducted a case control study on 264 subjects (103 cases and 161 controls) who were recruited from a tertiary hospital located in Karachi, Pakistan. Genomic DNA was extracted from peripheral blood using a commercial kit method, and the VDR-Cdx2 polymorphism was genotyped using tetraprimer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method. Pearson chi square test was used to assess the association between VDR-Cdx2 genotype and breast cancer while genotype distribution in controls was evaluated by Hardy-Weinberg equilibrium (HWE). Breast cancer risk was calculated using odds ratios and 95% confidence intervals. Results The genotype distribution in the control group was in HWE (p > 0.05) for the VDR-Cdx2 polymorphism. A non-significant association was observed between VDR cdx2 polymorphism and breast cancer, however the GG genotype was at risk (OR = 1.832, 95% CI = 0.695–4.828) of developing breast cancer. Conclusion The GG genotype of Cdx2-VDR gene polymorphism may increase the risk of developing breast cancer in young female patients in South Pakistan. Further investigations examining additional single nucleotide polymorphisms (SNPs) in VDR are required to assess their relationships with breast cancer.

Elevated levels of chemerin, leptin, and interleukin-18 in gestational diabetes mellitus.

Abstract Objective: We aimed to assess the levels of adipokine and their relation to gestational diabetic related clinical phenotypes and fetal growth parameters. Material and methods: International Association of the Diabetes and Pregnancy Study criteria was used to classify gestational diabetic cases (n = 208) and euglycemic controls (n = 300). ELISA assays were performed for insulin, chemerin, leptin, and interleukin-18 (IL-18). Mann–Whitney U test, Chi-square/Fisher exact test, multiple regression analyses, and ROC curves were applied with significant p values of <0.05. Results: Levels of chemerin, IL-18, and leptin were seven-, four-, and five-folds higher in cases versus controls, respectively (p < 0.01). The adipokine showed strong positive correlation with fasting blood glucose, homeostasis model assessment of insulin resistance, and fetal weight (p < 0.01). Odds of GDM association remained significant for chemerin (OR 1.522; 1.097–2.110) and leptin (OR 2.579; 1.503–4.425) while all associations were lost for IL-18 (p > 0.05) after multiple adjustments. Raised chemerin levels were identified in 96% cases (n = 201) employing the proposed cut off value >15.49 ng/ml. Conclusion: High chemerin and leptin levels are seen in GDM which may be associated with subclinical inflammation suggesting a role in development of insulin resistance.

Screening of subclinical hypothyroidism during gestational diabetes in Pakistani population

Abstract Objective: The increased prevalence of adverse effects of altered thyroid functions in pregnancy inspired us to study the frequency of subclinical hypothyroidism (SCH) and the relationship with glycaemic control and foetal weight in pregnant females with and without gestational diabetes mellitus (GDM) in Pakistani population. Patients and methods: Five hundred and eight pregnant females were enrolled and grouped as per the International Diabetes Association criteria into GDM (n = 208) and healthy control (n = 300). Random blood glucose (RBG), thyroid function tests, anthropometric analysis and foetal ultra sound scans were performed on all study subjects. Data were analysed using Mann–Whitney U test and Chi-square test wherever applicable. Spearman correlation and multiple regression analysis were performed. p values of <0.05 was considered significant. Results: A total of 61.5% GDM subjects depicted SCH with normal circulating T4 and T3 versus 6.0% healthy controls (p-value < 0.001). Moreover, TSH remained independently associated with RBG (r = 0.109; p < 0.05), poor glycaemic control (r = 0.227; p < 0.001) and negatively associated with foetal growth (r = −0.206; p < 0.001). Conclusion: The detection of high TSH with normal T3 and T4 in females with GDM strongly emphasises the need of thyroid screening as a routine in all antenatal clinics.

Association between Vitamin D receptor (Cdx2, Fok1, Bsm1, Apa1, Bgl1, Taq1, and Poly (A)) gene polymorphism and breast cancer: A systematic review and meta-analysis

The purpose of this systemic review and meta-analysis was to examine the relationship between VDR gene polymorphisms and breast cancer. Literature was searched through PubMed database, Google scholar, and the web of knowledge from December 2015 to January 2017 and consists of 34 studies (26,372 cases and 32,883 controls). All statistical measures were done using STATA version 11.2. The heterogeneity among studies was tested using I2 statistics. Mantel–Haenszel method and DerSimonian–Laird method were used to combine data from studies using both random-effect model and fixed-effect model, respectively. Potential publication bias was evaluated by Egger’s test. Sensitivity analysis was also performed to evaluate the quality and consistency in results. The results of this meta-analysis revealed that VDR gene polymorphisms (Bsm1 bb vs BB; SOR = 1.18, 95% CI = 1.054–1.322, Apa1 aa vs AA; SOR = 1.18, 95% CI = 0.87–1.59, Poly (A) LL vs SS; SOR = 1.41, 95% CI = 1.06–1.88, Fok1 ff + Ff vs FF; SOR = 1.25, 95% CI = 0.896–1.759, Apa1 aa+Aa vs AA; SOR = 1.13, 95% CI = 0.95–1.35, Poly (A) LL + LS vs SS; SOR = 1.19, 95% CI = 1.00–1.43, Poly (A) L vs S; SOR = 1.18, 95% CI = 1.03–1.35) are associated with the breast cancer. Cdx2, Bgl1, and Taq1 do not show association with breast cancer. Thus, the finding of this meta-analysis concluded that VDR Bsm1, Apa1, Fok1, and Poly (A) gene polymorphisms may be susceptible for breast cancer development.

Characterization of H5N1 highly pathogenic avian influenza viruses isolated from poultry in Pakistan 2006–2008

Nine avian influenza viruses (AIV), H5N1 subtype, were isolated from dead poultry in the Karachi region of Pakistan from 2006 to 2008. The intravenous pathogenicity indices and HA protein cleavage sites of all nine viruses were consistent with highly pathogenic AIV. Based on phylogenetic analysis of the HA genes, these isolates belong to clade 2.2 and both the HA and NA are closely related to each other (nucleotide identities above 99.0%) and to other Middle Eastern H5N1 AIV isolates (nucleotide identities above 98.0%). The phylogenetic data suggest that the virus in both epornitics of H5N1 HPAIV in commercial poultry in the Karachi region of Pakistan between 2006 and 2008 were from a very closely related source, however, there is inadequate epidemiological data to determine what the reservoir was for the virus between the 2006 and 2007 outbreaks other than that there was a single introduction into the region.

Correlation of ABH blood group antigens secretion with Helicobacter pylori infection in Pakistani patients

A and B blood group antigens are fucosylated carbohydrate present on human erythrocytes and body secretions. Their presence in body secretions depends on the expression of a dominant allele of secretor gene FUT2 and is correlated with susceptibility to various infectious and non‐infectious diseases. We investigated the correlation of blood group and ABH antigen secretion with Helicobacter pylori infection and gastroduodenal symptoms and analysed the distribution of babA gene among ABH secretors and non‐secretors.

Molecular Characterization of Pakistani Field Isolates of Infectious Bursal Disease Virus

Abstract The reverse transcriptase-polymerase chain reaction followed by restriction fragment length polymorphism (RT-PCR/RFLP) technique was used to identify and characterize Pakistani field isolates of infectious bursal disease virus (IBDV). These isolates have caused heavy losses to the poultry industry (mortality up to 60%) during the period between 1999 and 2005. Ten samples (five local isolates and five commercial vaccines) were examined for IBDV. Nine samples were positive for IBDV as evidenced by the amplification of the 743-bp region of the VP2 gene by RT-PCR. The RT-PCR products were subjected to restriction enzyme digestion with BstNI, MboI, and SspI. The RFLP profiles of all samples on digestion with the MboI enzyme yielded a fragment size of 229 and 362 bp except for vaccine strain Bursine Plus, which yielded a profile of 229 and 480 bp. However, digestion with BstNI yielded two distinct RFLP patterns. The first profile was detected in field isolates ML-1/SPVC/2001 and NP2/SPVC/2002 with four fragments of 119, 154, 172, and 209 bp, resembling RFLP profiles of molecular group 4 isolates. NL-3/SPVC/2003, NK-4/SPVC/2004, and NPK-5/SPVC/2005 generated a different RFLP profile with fragments of 119, 172, and 424 bp, resembling the profiles of molecular group 6 isolates. However, all the field and vaccine strains showed the absence of SspI restriction sites in their genome. It can be concluded that the Pakistani isolates can be grouped in molecular groups 4 and 6 of IBDV.

Complete Genome Sequence of a Velogenic Newcastle Disease Virus Strain Isolated from a Clinically Healthy Exotic Parakeet (Melopsittacus undulatus) in Pakistan

ABSTRACT The complete genome sequence of a virulent Newcastle disease virus (vNDV) strain isolated from an exotic parakeet (Melopsittacus undulatus) is described here. The virulent strain parakeet/Pak/R-Pindi/SFR-16/2016 was isolated from a bird reared as a pet in the province of Punjab in the northern region of Pakistan in 2016. Phylogenetic analysis classified the isolate as a member of NDV class II, subgenotype VIIi, in genotype VII.