GSTP1 Ile105Val polymorphism in Serbian patients with pancreatic diseases

Cilj ove studije bio je da se odredi učestalost polimorfizma Ile105Val u genu za glutation S-transferazu P1 (GSTP1) i proceni njegov uticaj na rizik za obolevanje od pankreasnih bolesti u srpskoj populaciji. Studija je obuhvatila 157 pacijenata sa najčešćim bolestima pankreasa: 47 sa karcinomom pankreasa, 50 sa hroničnim pankreatitisom i 60 sa dijabetes melitusom tipa 2, kao i 107 zdravih ispitanika. Prisustvo polimorfizma Ile105Val u genu za GSTP1 je analizirano metodom PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism). Učestalost alela 105Val je bila niža kod pacijenata sa karcinomom pankreasa (24,5%) i hroničnim pankreatitisom (24,0%) i neznatno povišena kod pacijenata sa dijabe tes melitusom tipa 2 (31,7%) u odnosu na učestalost kod zdra vih ispitanika (29,9%), ali razlike nisu bile statistički zna čaj ne. Učestalost pojedinih genotipova polimorfizma Ile105Val se razlikovala među analiziranim grupama, ali razlike takođe nisu bile statistički značajne. Samo nekoliko studija se do sada bavilo ulogom GSTP1 Ile105Val polimorfizma u bolestima pankreasa i uglavnom su dale oprečne rezultate. Značaj GSTP1 Ile105Val polimorfizma za bolesti pankreasa još uvek nije razjašnjen i potrebna su dalja istraživanja da bi se ispitala njegova uloga u pankreasnom tkivu. .The aim of the current preliminary case-control study was to identify glutathione S-transferase P1 (GSTP1) Ile105Val allele and genotype frequency and to evaluate its impact on susceptibility to pancreatic diseases in a Serbian population. This study has encom passed 157 patients with three major types of chronic pancreatic pathology: 47 with pancreatic cancer, 50 with chronic pancreatitis and 60 with type 2 diabetes mellitus, as well as 107 healthy individuals. The presence of GSTP1 Ile105Val polymorphism was analyzed using a PCR-RFLP method. Allele 105Val was less frequent in patients with pancreatic cancer (24.5%) and chronic pancreatitis (24.0%) and slightly more frequent in patients with type 2 diabetes mellitus (31.7%) in comparison to healthy individuals (29.9%), but the differences were not statistically significant. Distribution of Ile105Val polymorphism genotypes differed between the analyzed groups, but differences were also not statistically significant. There are only a few studies regarding the role of GSTP1 Ile105Val polymorphism in pancreatic diseases and their results are inconsistent. The significance of GSTP1 Ile105Val polymorphism for pan creatic pathology remains unclear and further studies are needed in order to elucidate its role in pancreatic diseases.

Prevalence of S and Z alpha 1-antitrypsin mutations in patients with pancreatic diseases in Serbian population

Jedan od osnovnih izazova u proučavanju patologije bolesti pankreasa predstavlja dalje razjašnjavanje uloge proteaza i antiproteaza, zbog toga što poremećena ravnoteža između njih može dovesti do oštećenja pankreasa. Alfa 1-antitripsin (AAT) je jedan od najvažnijih inhibitora proteolitičkih enzima u serumu, među kojima su i enzimi pankreasa: tripsin, himotripsin i elastaza. Pretpostavlja se da mutacije u AAT genu mogu da utiču na pojavu i razvoj bolesti pankreasa. Prisustvo najčešćih mutacija u AAT genu, označenih kao Z i S, analizirano je u 160 pacijenata sa bolestima pankreasa (50 pacijenata sa kancerom pankreasa, 50 pacijenata sa hroničnim pankreatitisom i 60 pacijenata sa dijabetesom tipa 2) i u 129 zdravih osoba. Prisustvo mutacija detektovano je analizom dužina restrikcionih fragmenata. Jedan pacijent sa kancerom pankreasa je bio heterozigotni nosilac Z mutacije, kao i jedan pacijent sa dijabetesom tipa 2. Jedan pacijent sa hroničnim pankreatitisom je bio heterozigotni nosilac S mutacije. Dve najčešće mutacije u AAT genu su bile statistički značajno učestalije kod pacijenata sa bolestima pankreasa (3 / 160 pacijenata, alelska frekvencija 0,9%) nego u kontrolnoj grupi (1 / 129 osoba, alelska frekvencija 0,4%). Rezultati ove studije, koje ukazuju na moguću povezanost Z i S mutacija sa umerenim povećanjem rizika za razvoj bolesti pankreasa.One of the key points in research of pancreatic disease pathology is further elucidation of the role of proteases and antiproteases, since their imbalance can lead to pancreatic injury. Alpha 1-antitrypsin (AAT) is one of the most important serum inhibitors of proteolytic enzymes, including pancreatic enzymes trypsin, chymotrypsin and elastase. It is speculated that mutations in the AAT gene may influence the onset and the development of pancreatic disease. The presence of the most common AAT mutations Z and S was analyzed in 160 patients with pancreatic diseases (50 patients with pancreatic cancer, 50 patients with chronic pancreatitis and 60 patients with type 2 diabetes mellitus) and 129 healthy individuals by PCR-mediated site-directed mutagenesis (PSM) method. One patient with pancreatic cancer was found to be a carrier of Z mutation, as well as one patient with type 2 diabetes mellitus. One patient with chronic pancreatitis was found to be a carrier of S mutation. The common AAT mutations were statistically significantly over-represented in patients with pancreatic diseases (3 of 160 patients, allelic frequency 0.9%) than in the control group (1 of 129 individuals, allelic frequency 0.4%). The results of this study, requiring confirmation, suggest that common AAT mutations Z and S may be associated with a modest increase in susceptibility to the development of pancreatic disease

Melatonin Action in Type 2 Diabetic Parotid Gland and Dental Pulp: In Vitro and Bioinformatic Findings

Type 2 diabetes mellitus (T2DM) is associated with functional deterioration of the salivary gland and dental pulp, related to oxidative stress. The aim was to integrate experimental and bioinformatic findings to analyze the cellular mechanism of melatonin (MEL) action in the human parotid gland and dental pulp in diabetes. Human parotid gland tissue was obtained from 16 non-diabetic and 16 diabetic participants, as well as human dental pulp from 15 non-diabetic and 15 diabetic participants. In human non-diabetic and diabetic parotid gland cells (hPGCs) as well as in dental pulp cells (hDPCs), cultured in hyper- and normoglycemic conditions, glial cell linederived neurotrophic factor (GDNF), MEL, inducible nitric oxide synthase (iNOS) protein expression, and superoxide dismutase (SOD) activity were measured by enzyme-linked immunosorbent assay (ELISA) and spectrophotometrically. Bioinformatic analysis was performed using ShinyGO (v.0.75) application. Diabetic participants had increased GDNF and decreased MEL in parotid (p < 0.01) and dental pulp (p < 0.05) tissues, associated with increased iNOS and SOD activity. Normoglycemic hDPCs and non-diabetic hPGCs treated with 0.1 mM MEL had increased GDNF (p < 0.05), while hyperglycemic hDPCs treated with 1 mM MEL showed a decrease in up-regulated GDNF (p < 0.05). Enrichment analyses showed interference with stress and ATF/CREB signaling. MEL induced the stress-protective mechanism in hyperglycemic hDPCs and diabetic hPGCs, suggesting MEL could be beneficial for diabetes-associated disturbances in oral tissues

Importance of MMP-2 and MMP-9 gene polymorphism in the development of microvascular complications in type 2 diabetes patients

Vaskularne komplikacije su vodeći uzrok morbiditeta i mortaliteta kod pacijenata sa diabetes mellitusom...Vascular complications are leading cause of increased morbiditz and mortalitz of diabetic patients..

Importance of MMP-2 and MMP-9 gene polymorphism in the development of microvascular complications in type 2 diabetes patients

Vaskularne komplikacije su vodeći uzrok morbiditeta i mortaliteta kod pacijenata sa diabetes mellitusom...Vascular complications are leading cause of increased morbiditz and mortalitz of diabetic patients..

MTHFR C677T polymorphism in chronic pancreatitis and pancreatic adenocarcinoma

Chronic pancreatitis and pancreatic adenocarcinoma are extensively studied as common and potentially lethal disorders. However, their Causes and genetic background in most cases remain unclear. The C677T polymorphism in 5',10'-methylenetetrahydrofolate reductase (MTHFR) gene may modulate the risk of pancreatic disorders. In this Study, we tested whether MTHFR C677T polymorphism is associated with chronic pancreatitis and pancreatic adenocarcinoma in the Serbian population. DNA was extracted from blood samples of 51 chronic pancreatitis patients, 21 pancreatic adenocarcinoma patients, and a control group consisting of 50 healthy smokers. The MTHFR C677T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Although, no statistically significant differences were observed in the distribution of MTHFR genotype or allele frequencies between patients and control groups, the results showed an increased frequency of homozygotes for MTHFR C677T polymorphisrn in chronic pancreatitis patients ( 14%) and a decreased frequency in pancreatic adenocarcinoma patients (5%) in comparison to the control group (8%). We speculate that the MTHFR C677T polymorphism Could act as a possible risk factor for chronic pancreatitis and a possible protective factor in pancreatic adenocarcinoma. This observation needs further investigation in prospective Studies on a larger number of patients, in which the effect of other genetic and environmental factors should also be taken into consideration