RESUMO
BACKGROUND: Gastric cancer (GC) is the third most common cancer in India and is mediated by multiple genetic, epigenetic and environmental risk factors. A single nucleotide polymorphism rs3025058 at − 1171 of the stromelysin‑1 (matrix metalloproteinase [MMP]‑3) promoter is resulting due to insertion/deletion of adenine thought to have an impact on increasing the risk for tumor formation. AIM: This study is aimed to understand the role of stromelysin‑1 rs3025058 (−1171, 5A/6A) promoter polymorphism in the etiology of GC in Indian population. MATERIALS AND METHODS: Genomic DNA was isolated from blood samples of the GC patients and controls. The genotyping of stromelysin‑1 rs3025058 (−1171, 5A/6A) promoter polymorphism was carried out by amplification refractory mutation system‑polymerase chain reaction method followed by agarose gel electrophoresis. RESULTS: The frequency of 5A/5A, 5A/6A, and 6A/6A genotypes in GC patients were 7.69%, 76.92%, and 15.38%, while in controls were 5.31%, 86.73%, and7.96%, respectively. There was a significant difference in the distribution of 5A/6A genotype in patients compared to the controls (P < 0.05). CONCLUSION: This study showed an increased frequency of heterozygotes for stromelysin‑1 rs3025058 and thought to be involved in the etiology of GC.
RESUMO
Background:Cu-Zn superoxide dismutases are antioxidative defensive enzymes that catalyze the reduction of superoxide anions to hydrogen peroxide. Aim:The study focuses on the association of electromorph of superoxide dismutase with duodenal ulcers, which result due to an imbalance between aggressive and defensive factors. Materials and Methods:Endoscopically confirmed 210 duodenal ulcer patients and 185 healthy individuals for comparative analysis were considered for the present study. Phenotyping of superoxide dismutase was carried out by subjecting the RBC membranes to polyacrylamide gel electrophoresis, using appropriate staining protocols. Results:Statistical analysis of SOD phenotypes revealed a significant increase of SOD A*2 allele and Superoxide dismutases (SOD) 2-2 phenotype in duodenal ulcer group. Among these individuals, a predominance of Helicobacter pylori infection was observed. The increased preponderance of homozygotes can be explained on the basis of reduced and altered enzyme activity, which may lead to disturbance in homeostasis of antioxidant/oxidant culminating in high lipid peroxidative gastric mucosal tissue damage and ulceration. No variation in the distribution of SOD phenotypes with respect to Helicobacter pylori indicates the role of Mn-SOD rather than Cu-Zn SOD in the Helicobacter pylori infected cases as reported earlier. Conclusions:Superoxide dismutase as a genetic marker / gene modifier, encoding for an antioxidant enzyme in maintaining tissue homeostasis of the gastric mucosa is discussed.
RESUMO
Background: Duodenal ulcer (DU) is a multifactorial disorder with different etiological and pathogenetic mechanisms. Evidence for the role of genetic factors such as familial aggregation, twin studies, ABO blood groups, ABH nonsecretor status and hyperpepsinogenemia have been reported in DU. Genetic heterogeneity of cases with familial incidence will provide information regarding the association of qualitative and quantitative traits. Aim: Hence, the present study is envisaged at identifying the segregant and deviant groups based on parental phenotypes and their association with other quantitative markers. Materials AND Methods: 62 out of 462 endoscopically confirmed duodenal ulcer cases were considered for the analysis of genetic heterogeneity. This was resolved through the calculation of genetic risk estimates of sporadic cases in multiplex families based on different modes of inheritance and variation in associated genetic and biochemical markers. Results: Mean age at onset in simplex and multiplex cases was found to vary indicating the presence of genetic heterogeneity in the expression of the disease. Segregant and deviant groups were identified based on mortons probability risk estimates and examined for the possible association of qualitative and quantitative markers such as pepsinogen phenotype, serum and tissue pepsinogen levels, cathepsin E, malondialdehyde and ceruloplasmin levels. Conclusions: The study thus highlighted the presence of genetic heterogeneity in the expression of the disease. The risk factors associated with segregant type were normal serum and tissue pepsinogen levels increased malondialdehyde levels and association of AC phenotype while the deviant group was characterized by early age at onset with hyper pepsinogenemia and reduced cathepin E levels.
RESUMO
BACKGROUND: Duodenal ulcers are mucosal erosions that penetrate into the muscularis propria of the duodenum. They are a result of an imbalance between aggressive and defensive factors. Various environmental factors like Helicobacter pylori infection, addictions to smoking and alcohol etc. and genetic factors have been reported to be associated with duodenal ulceration. Alpha-1-antitrypsin was studied for its role as a genetic marker and specific allelic association to protein functioning and alteration. Serum samples from 185 normal subjects and 210 duodenal ulcer cases were typed for the phenotypes following PAGE (polyacrylamide gel electrophoresis) and immunofixation using specific commercial antisera with appropriate staining protocols. In general, 'M' allele of alpha-1-antitrypsin was found to be predominant in healthy normal subjects, with the gene frequencies being 0.679 (M), 0.299 (Z) and 0.0214 (S). Whereas in duodenal ulcer cases, Z and S alleles were found to be predominant with a significant association of MS, ZZ and MZ phenotypes (c2sub : 49.98) and the gene frequencies being 0. 113 (M), 0. 347 (Z) and 0.506 (S). Predominance of Z and S alleles indicates that these alleles may encode for reduced synthesis of alpha-1-antitrypsin, hence decreased neutralization of proteases like trypsin and chymotrypsin inhibited by alpha-1-antitrypsin, thereby resulting in ulcers. The study highlights the association of Z and S alleles of the potent protease inhibitor alpha-1-antitrypsin and also suggests its role as a genetic marker in ulcerogenesis.
RESUMO
The association of the ABO antigen-antibody titres with the ABH secretor status in duodenal ulcers was examined in a sample of 196 patients and 182 healthy controls. The risk for group A and group B patients depended upon the strengths of the antigens and the ABH secretor status. Further the risk was high for low antibody titres in non-secretor patients than in secretor patients. Increased demand on the antibodies for mucoprotection in the absence of the A and B antigens in the gastro-intestinal mucosa or insufficient production of antibody by the lymphocytes could be the possible reasons.