Decoding type 2 diabetes mellitus genetic risk variants in Pakistani Pashtun ethnic population using the nascent whole exome sequencing and MassARRAY genotyping: A case-control association study.

Genome-wide association studies have greatly increased the number of T2DM associated risk variants but most of them have focused on populations of European origin. There is scarcity of such studies in developing countries including Pakistan. High prevalence of T2DM in Pakistani population prompted us to design this study. We have devised a two stage (the discovery stage and validation stage) case-control study in Pashtun ethnic population in which 500 T2DM cases and controls each have been recruited to investigate T2DM genetic risk variants. In discovery stage Whole Exome Sequencing (WES) was used to identify and suggest T2DM pathogenic SNPs, based on SIFT and Polyphen scores; whereas in validation stage the selected variants were confirmed for T2DM association using MassARRAY genotyping and appropriate statistical tests. Results of the study showed the target positive association of rs1801282/PPARG (OR = 1.24, 95%Cl = 1.20-1.46, P = 0.010), rs745975/HNF4A (OR = 1.30, 95%Cl = 1.06-1.38, P = 0.004), rs806052/GLIS3 (OR = 1.32, 95%Cl = 1.07-1.66, P = 0.016), rs8192552/MTNR1B (OR = 1.53, 95%Cl = 0.56-1.95, P = 0.012) and rs1805097/IRS-2 (OR = 1.27, 95%Cl = 1.36-1.92, P = 0.045), with T2DM; whereas rs6415788/GLIS3, rs61788900/NOTCH2, rs61788901/NOTCH2 and rs11810554/NOTCH2 (P>0.05) showed no significant association. Identification of genetic risk factors/variants can be used in defining high risk subjects assessment, and disease prevention.

Antecedent infections, recent developments and future directions in Guillain-Barré syndrome.

The Guillain-Barré syndrome is an autoimmune polyradiculoneuropathy causing symmetrical weakness of limbs. After poliomyelitis, it is the second most common cause of paralysis, with an annual incidence of 0.84-1.91 per 100,000 individuals. The syndrome affects both men and women, showing a male preponderance. Campylobacter jejuni, epstein-barr virus, cytomegalovirus, mycoplasma pneumoniae and haemophilus influenzae are amongst the most common causative agents of Guillain-Barré syndrome. Several immunological and genetic factors have been recognised as the risk factors. Human leukocyte antigen, cluster of differentiation 1, and tumour necrosis factor-alpha alleles are among the frequently investigated loci in Guillain-Barré syndrome. Genome-wide association studies have found no significant association of Guillain-Barré syndrome with common variants. Many vaccines against Campylobacter jejuni infection have been proposed, but there are concerns about the efficacy and safety of these vaccines. So far, there is no approved vaccine against Campylobacter jejuni.

Systematic Literature Review on Indicators Use in Safety Management Practices among Utility Industries.

BACKGROUND: Workers in utility industries are exposed to occupational accidents due to inadequate safety management systems. Accordingly, it is necessary to characterize and compare the available literature on indicators used in safety management practices in the utility industries. METHODS: The systematic literature review was based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. This study considered 25 related studies from Web of Science and Scopus databases. RESULTS: Further review of these articles resulted in three mains performance indicators; namely, driven leading indicators, observant leading indicators, and lagging indicators consisting of 15 sub-indicators. CONCLUSIONS: Future studies should consider researching a more comprehensive range of utility industries, measuring subjective and objective indicators, integrating risk management into safety management practices, and validating the influence of leading indicators on safety outcomes. Further, researchers recommend including accidents, fatalities, lost time injuries, and near misses in safety outcomes.

Association of ATM, CDH1 and TP53 genes polymorphisms with familial breast cancer in patients of Khyber Pakhtunkhwa, Pakistan.

Background: Genetic studies play a significant role in understanding the underlying risk factors of breast cancer. Polymorphism in the tumor suppressor gene TP 53, CDH1 and ATM genes are found to increase susceptibility for breast cancer globally. Objective: This study aimed to identify/analyze the contribution of genetic polymorphisms in the breast cancer candidate genes ATM, TP53 and CDH1 that may be associated with familial breast cancer risk in the Khyber Pakhtunkhwa population. Subjects and Methods: In the present case-control study, Whole Exome Sequencing (WES) of the 100 breast cancer patients and 100 ethnic controls were performed for the selected genes in the target population. Results: Of the studied variants rs3743674 of the CDH1 gene (crude P=0.014 and adjusted p=0.000) evident significant association with breast cancer in Pakistani Pashtun population. Whereas TP53rs1042522 (crude P=0.251 and adjusted P=0.851) and ATM rs659243 (crude p=0.256 and adjusted p=0.975) showed no or negative association with breast cancer in study population. Conclusion: The present study demonstrates that CDH1rs3743674 polymorphism is associated with elevated breast cancer risk in the Pashtun ethic population of Khyber Pakhtunkhwa.

Genetic susceptibility to esophageal cancer due to CYP1A1 gene variant rs4646903 in tobacco addicted patients of Pashtun ethnicity: a case control study in Khyber Pakhtunkhwa province of Pakistan.

The purpose of this study was to evaluate associations of the CYP1A1 gene variant rs4646903 polymorphism with the risk of developing esophageal cancer (EC). A case-control study was carried out in Pashtun population of Khyber Pakhtunkhwa province of Pakistan in which 140 hospital based EC cases and 196 population based healthy controls exposed to similar environmental conditions were included. A specific method based on the real time polymerase chain reaction (RT-PCR) was used to detect genotypes in case and control groups and results were then analyzed with SPSS version 20. In our population, individuals with CC and TC genotypes of the CYP1A1 rs4646903 polymorphism had significantly higher risk of EC (adjusted odds (OR): 15.709, 95%CI: 6.065-40.686, OR: 3.256 95%CI: 1.902-5.574 respectively). The 'C' allele was strongly associated with the disease (p< 0.0001). Adjusted OR was higher (1.5 times in C/C) in case of variant alleles that show the contribution of environmental and nutritional factors towards the development of EC. Our findings suggest that presence of the 'C' allele of rs4646903 (T>C) may be one of the risk alleles for EC susceptibility in Pashtun population.