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Genetic variations in a disintegrin and metalloprotease 12 (ADAM12) gene may contribute to develop Osteoarthritis (OA) that is characterized by cartilage matrix degradation and osteophytes formation. Therefore, the aim of present study was to analyze the association between the ADAM12 gene variants and knee OA predisposition. Tetra-primers ARMS-PCR was employed, to genotype the ADAM12 gene polymorphisms (rs1044122 and rs1871054) in 400 knee OA patients and equal number of age-matched controls. The association between ADAM12 gene variants and OA susceptibility was estimated using the Chi-square, logistic regression, haplotypes and linkage analyses. A significant association of rs1044122 (genotype: χ

Antibiotic resistance poses a serious threat to human and animal health. As a consequence, their use in conventional poultry feed may be replaced by non-antibiotic additives (alternatives to antibiotics, ATAs). Phytogenic feed additives and organic acids have been gaining considerable attention that could abate the proliferation of pathogenic bacteria and strengthen gut function in broiler chickens. The aim of this study was to evaluate the effects of phytogenic feed additives and organic acids on cecal microbial diversity using 16S rRNA amplicon sequencing of the V3-V4 region. In this study, 240 chicks were divided into five treatments comprising: a controlled basal diet (CON), antibiotic group (AB), phytogenic feed additives (PHY), organic acids (ORG) and a combination of PHY + ORG (COM). A distinctive microbial community structure was observed amongst different treatments with an increased microbial diversity in AB, ORG and COM (p ). The synergistic effects of PHY and ORG increased the population of beneficial bacteria that belonged to the phyla: Firmicutes, Bacteroides and Proteobacteria in the cecum. The presence of the species Akkermansia muciniphila (involved in mucin degradation) and Bacillus safensis (a probiotic bacterium) were noticed in COM and PHY, respectively. Clustering analysis revealed a higher relative abundance of similar microbial community composition between AB and ORG groups. In conclusion, treatments with PHY and ORG modified the relative abundance and presence/absence of specific microbiota in the chicken cecum. Hence, cecal microbiota modulation through diet is a promising strategy to reduce cross-contamination of zoonotic poultry pathogens.

Esophageal and lung Squamous Cell Carcinoma (SCC) pose a serious threat to health as they are amongst the most prevalent cancers in Pakistan. Increased metabolic and energy needs within the proliferating cancer cells results in hypoxia, affecting the homeostatic balance within the tumor microenvironment. Under these circumstances, key hypoxia-regulated genes like CA9 have major role in the survival and invasiveness of malignant tumors. This study targeted the single nucleotide polymorphism rs2071676 in CA9 to find its association with the risk of ESCC and LSCC. The non-synonymous function of this polymorphism cause the base pair to change from guanine to adenine that changes the amino acid associated with the signal peptide domain of CAIX protein from valine to methionine. Blood samples and data from 127 cases with ESCC, 73 patients with LSCC and from their age and sex-matched healthy controls were collected. Genomic DNA were extracted through standard phenol-chloroform method. Assessment of targeted polymorphism was performed through tetra-primer Amplified Refractory Mutation System Polymerase Chain Reaction (t-ARMS PCR). Pearson’s chi-square value gave statistically significant association of the SNP with LSCC (χ2 = 47.104) and ESCC (χ2 = 87.804), both with p

Pyrethroid (PYR) is a class of pesticide which was frequently applied in agricultural fields of Sanghar in Pakistan. Consistent and over use of PYR may lead to health effects on workers who are occupationally exposed to pesticides every day. For assessment of PYR toxicity, Cytochrome-P450 (CYP1A1) and Glutathione–S-transferase P1 (GSTP1) code for xenobiotic metabolizing enzymes (XME) were investigated in Sanghar exposed studied population. To execute the case-control study, a total of 200 blood samples from PYR-exposed and control subjects were collected. Prior informed consent was taken from all the subjects. For determination of genetic variations, CYP1A1 (rs1048943) and GSTP1 (rs1695) regions were amplified using polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP). Resolved bands were visualized on 2 % agarose gel. Results indicated that in CYP1A1 polymorphism (rs1048943) there was no significant association between CYP1A1 genotypes AA, AG, GG and PYR toxicity (ϰ2= 2.03, p > 0.05) in exposed subjects. However, the impact of mutant allele G was further evaluated by genetic models, which demonstrated that G allele may show a risk for CYP1A1gene susceptibility to PYR exposure (OR: 8.608; CI: 1.056–70.172) p

BACKGROUND Coronary artery disease (CAD) is a leading cause of mortality in Pakistan and also worldwide. Vitamin D receptor (VDR) regulates the transcription of many genes and has a significant impact on inflammation and the morphology of cardiac cells. Genetic variation in the VDR gene such as the TaqI polymorphism (rs731236) may have an impact that causes adverse effects. Accordingly, it is important to determine possible association of the TaqI polymorphism (rs731236) with CAD. METHODS The study included blood samples from 1016 subjects: 516 from CAD patients and 500 from age- and gender-matched controls. Genomic DNA was extracted by standard salting out method. Targeted variation was amplified by an allele-specific polymerase chain reaction (PCR). PCR products were examined and genotyped on agarose gel electrophoresis represented by an amplified product size of 148 bp followed by Sanger sequencing to validate variations. RESULTS Serum vitamin levels, as observed using enzyme-linked immunosorbent assay, were found to be insufficient in both CAD patients (20.52 ± 0.06 ng/ml) and controls (21.6981 ± 0.05 ng/ml). The TaqI polymorphism (rs731236) T>C was found to be significantly associated with CAD (p

Chemokine CC receptor type 5 (CCR5) is a cell surface receptor that has high affinity for chemotropic cytokines called chemokines. The CCR5 gene contains a 32 base pairs (bp) deletion (CCR5Δ32). This deletion may result in a malformed and nonfunctional receptor, reported to be responsible for the development and dissemination of different cancers. CCR5Δ32 exists in two allelic forms i.e. deletion (D) and wild type (WT). This study aims to detect the role of CCR5Δ32 in breast cancer development. Blood samples were collected from breast cancer patients (330) and controls of same gender (306). Along with this histopathologically diagnosed malignant tissue samples were also excised from breast lesions of 100 patients. Genetic variations within the blood and tissue samples were examined by PCR then observed through gel electrophoresis and confirmed by direct DNA sequencing. Obtained DNA sequences were aligned and analyzed by MEGA6 software. Genotypic and association analyses were done by SPSS software version 17.0. Deletion of 32 bp in CCR5 gene has been analyzed. Genotypic variations of CCR5Δ32 are; homozygous wild type (WT/WT), heterozygous deletion (WT/D) and homozygous deletion (D/D). Statistical analyses of CCR5Δ32 data revealed that WT/D was significantly higher in blood samples of breast cancer patients (7.27% (24/330)) as compare to controls (1.30% (4/306)). In tumor tissue samples WT/WT being the most frequent genotype (99.00% (99/100)) with 1.00 (1/100) of D/D which suggested that it may be acquired. Hence, association analysis showed that CCR5Δ32 is positively associated with breast cancer in Pakistan (p

Introduction: Congenital heart diseases (CHD) are one of the neglected and challenging areas in undeveloped countries. In Pakistan approximately 40-50,000 children are affected annually. A majority of these patients belongs to rural areas where properly medical facilities are out of reach. In the etiology of these diseases genetic profile, consanguinity and other factors should be examined carefully. The current study aims to check the genetic manipulations in patients for the NKX 2.5 gene specifically the untranslated gene of this gene. NKX 2.5, a transcription factor and first progenitor in cardiac formation, it encodes 324 amino acid and contains a homeodomain (142-200aa) which is highly conserved among vertebrates. To date, no data is available about the mutations in this gene responsible for CHD in Pakistani population. Material and Methods: A cohort of 225, CHD patients who were registered at National Institute of Cardiovascular Diseases (NICVD) from 2006-2009 were included in the study; these are non-syndromic and sporadic cases. Healthy 200 controls were also included with informed consents and detail family history was obtained. DNA was extracted and NKX 2.5 gene was amplified and sequenced to check mutations. Results: The mean age for patients TOF (2.97±1.21), PDA (2.95±2.55), D-TGA (1.84±2.26) and for controls (3.14±1.82) .In present study, two UTR alterations have been reported for NKX 2.5 one at 5' and other at 3'.In our study we look social and genetic aspects for these diseases. Conclusion: CHD is a major cause of child death in the first year of life. Our study concludes a few aspects and will broaden it to other genes as it is a need to find etiology of these diseases and to combat it with the modern genetic therapeutics.