Heterozygosity of stromelysin‑1 (rs3025058) promoter polymorphism is associated with gastric cancer.

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.

Association of matrix metalloproteinase -7 (-181A/G) promoter polymorphism in chronic pancreatitis.

Background & objectives: Chronic pancreatitis is progressive and irreversible destruction of the pancreas. Matrix metalloproteinase-7 (MMP-7) is a secreted matrilysin, which contributes to angiogenesis and breakdown of basement membranes of pancreatic tissues. The present study was aimed to investigate the association of MMP-7 −181A/G (rs11568818) gene promoter polymorphism in patients with chronic pancreatitis. Methods: A total of 100 chronic pancreatitis patients and 150 unrelated healthy individuals were included in this case control study. The genotyping of the MMP-7 gene (− 181 A/G) (rs11568818) was carried out based on PCR-RFLP. The serum levels of MMP-7 were determined by ELISA. Association between genotypes and chronic pancreatitis was examined by odds ratio (OR) with 95% confidence interval (CI). Results: The frequencies of the genotypes in promoter of MMP-7 were AA 49 per cent, AG 25 per cent and GG 26 per cent in chronic pancreatitis patients and AA 53 per cent, AG 38 per cent and GG 9 per cent in control subjects. Frequency of MMP-7 −181GG genotype and − 181G allele was significantly associated with chronic pancreatitis compared to healthy subjects [OR = 1.58 (95% CI: 1.06 –2.36), p =0.019]. There was no significant difference in the serum MMP-7 levels in the patients compared to control subjects. Interpretation &conclusions: The present study revealed a significant association of MMP-7 -181A/G (rs11568818) GG genotype with chronic pancreatitis patients, indicating its possible association with the disease.

Hidden magicians of genome evolution.

Transposable elements (TEs) represent genome’s dynamic component, causing mutations and genetic variations. Transposable elements can invade eukaryotic genomes in a short span; these are silenced by homology-dependent gene silencing and some functional parts of silenced elements are utilized to perform novel cellular functions. However, during the past two decades, major interest has been focused on the positive contribution of these elements in the evolution of genomes. The interaction between mobile DNAs and their host genomes are quite diverse, ranging from modifications of gene structure to alterations in general genome architecture and can be regarded as hidden magicians in shaping evolution of genomes. Some of the prominent examples that impressively demonstrate the beneficial impact of TEs on host biology over evolutionary time include their role in structure and functions of eukaryotic genomes.

TGF β1 -509 C/T Polymorphism in Uterine Fibroids.

Uterine leiomyomas/fibroids are the most common pelvic tumors of the female genital tract. Transforming growth factor beta (TGF β) family members are multi-functional cytokines that play a key role in cellular growth, proliferation and differentiation. The aim of this study was to investigate whether TGF β1 - 509 C/T polymorphism could be used as a susceptibility marker in Uterine fibroids pathogenesis. ARMS PCR was carried out for controls and patients (n=103) to identify the specific genotypes. Genotypes and allelic frequencies in both groups were compared. Proportions of C homozygote, heterozygote and T homozygote for TGF β1gene polymorphisms were 37.9%, 44.7%, 17.5% in the control individuals and 37%, 51.5%, 11.7% in the uterine fibroid patients. There was no significant difference between the controls and the patients thus indicating the tumor suppressor effect of TGF β1 in the early stages of tumor pathogenesis. The study was found to be in association with the earlier reported data wherein TGF β1 acts as tumor suppressor in the early stages and as a tumor promoter in the later stages of tumor pathogenesis.

Mosaic triple X syndrome in a female with primary amenorrhea.

Background: Turner's syndrome is the most common chromosomal abnormality in females, affecting 1 in 2,500 live female births. It is a result of absence of an X chromosome or the presence of a structurally abnormal X chromosome. Its most consistent clinical features are short stature and ovarian failure. Aim: The aim of the study was to report a rare case of mosaic triple X syndrome in a female with primary amenorrhea. Materials and Methods: The chromosomal analysis using GTG banding was carried out, which revealed a mosaicism with 45,XO/47,XXX chromosomal constitution. Fluorescent in situ hybridization was also carried out to further confirm the observation made in the study. Conclusion: The physical features presented by the female could be due to the 45,XO/47,XXX mosaicism and the karyotype analysis was consistent with the diagnosis and clinical symptoms. Triple X mosaicism was confirmed with conventional and molecular cytogenetic analysis.

Role of matrix metalloproteinase 3 gene promoter polymorphism in chronic pancreatitis.

Aim To study the role of 5A/6A polymorphism of matrix metalloproteinase (MMP-3) and their levels in the pathogenesis of chronic pancreatitis (CP). Methods One hundred and twenty CP patients and an equal number of age and sex-matched healthy controls were included in the study. Genotypes were determined for 5A/6A allele of MMP-3 gene by allele specific PCR (AS-PCR). The serum MMP-3 levels were estimated using sandwich ELISA method. Results The distribution of the genotypes of the 5A/6A polymorphism in both control and study patients was similar (p=0.523). Within the disease group, patients with older age, early onset of the disease, and addictions such as smoking and alcohol consumption had higher levels as compared to those who did not have these features. Conclusion We conclude that functional polymorphism of MMP-3 (5A/6A) is not associated with CP. However, the higher levels within the disease group indicate its possible role in the disease process.

Helicobacter pylori infection in relation to gastric cancer progression.

Gastric cancer is a major cause of cancer death worldwide, especially in developing countries. The incidence of gastric cancer varies from country to country, probably as a result of genetic, epigenetic, and environmental factors. H. pylori infection is considered as a major risk factor in the development of gastric cancer. However, the scenario varies in Asian countries, exhibiting a higher rate of H. pylori infection and low incidence of gastric cancer, which could be attributed to strain-specific virulence factors and host genetic makeup. In this review, we discuss the various virulence factors expressed by this bacterium and their interaction with the host factors, to influence pathogenesis.

Clinical and behavioural profile of a rare variant of klinefelter syndrome-48, XXXY.

Klinefelter’s syndrome is a sex chromosomal aneuploidy caused by an addition of X chromosome in males (47,XXY).Variants of this syndrome with X and Y polygamy are of rare occurrence. Here we describe a rare case of 48, XXXY Klinefelter’s variant from South India with a reported incidence of 1 per 17,000 to 1 per 50,000 male births. The presence of an extra X chromosome/s in these individuals has a great impact on the physical and cognitive functions, which could be attributed to gene dosage effects and genes involved in neurogenic development.

Epidemiology and genetics of dilated cardiomyopathy in the Indian context.

Background: Dilated cardiomyopathy (DCM) still remains to be a poorly understood and less analyzed group of cardiac-muscle disorders when compared to hypertrophic cardiomyopathy (HCM). Also, the vast clinical heterogeneity among the patients has rendered the small and isolated kindred studies less informative on the genetics and epidemiology of DCM. Aim of the study: The study aimed at understanding the epidemiology and genetics of DCMs in the Indian context. Materials and methods/ Statistical analysis: One hundred seven DCM patients and 105 healthy individuals were included in the study for epidemiological and genetic risk factor identification and to fit the possible mode of inheritance. Single's ascertainment methodology for segregation analysis and Penrose frequency estimates were followed to evaluate for the role of specific epidemiological factors in the disease etiology. Chi-square analysis was carried out to interpret the results statistically. Results and Conclusion: Our study suggests that epidemiological factors like gender, age at onset and vegetarian diet in conjunction with sarcomere gene mutations may play a role in the disease expression. Similarly, segregation analysis for the possible mode of inheritance showed a deviation from the autosomal dominant mode of inheritance, strengthening the underlying genetic heterogeneity of DCM.

Superoxide dismutase phenotypes in duodenal ulcers: A genetic marker.

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.

Genetic heterogeneity in duodenal ulceration.

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.

Malondialdehyde levels in patients with duodenal ulcer.

Malondialdehyde (MDA) is a stable product of lipid peroxidation of membrane lipids. In view of its role in membrane lipid damage in various inflammatory disorders, MDA levels were estimated in 83 duodenal ulcer patients and 48 controls. MDA levels were found to be significantly higher in duodenal ulcer patients as compared to controls (mean +/- SD 280.2 +/- 109.0 versus 216.5 +/- 81.4 nm/dL, p < 0.001). These increased levels of MDA may represent either the result of peroxidative damage in the disease process or a pathogenetic factor enhancing the risk for duodenal ulcer.