Indian Journal of Genetics and Molecular Research

Hereditary Angioedema (HAE) is characterized by recurrent attacks of submucosal or subcutaneous edema and is caused by mutations in gene SERPING1. We identified a novel heterozygous small deletion in SERPING1 using targeted exome sequencing in an HAE patient from an Indian family. The mutation c.491_502delAGACCAACATGG,p. Glu164_ Met167del, in exon 3 of SERPING1 gene is reported in the proband and her father but was not found in proband’s unaffected sibling and control samples. The mutation was classified as ‘Likely Pathogenic’ according to ACMG guidelines for interpretation of sequence variants. To the best of our knowledge, this is the first documented report for SERPING1 mutation in HAE type1 patients from India.

Mutation is an alteration that occurs in our DNA sequence, generally due to the error developed when the DNA is copied or as the result of environmental causes such as radiations like ultraviolet rays, cigarette smoke etc. On the whole, there are 3 kinds of DNA mutations, the base substitutions, the deletions and the additions. Mutation is the resource
of newness and it creates new forms of species, potentially instantaneously in a sudden jump. This was envisaged as a pouring evolution and limited by the contribution of mutations. Mutationism is one of the alternatives to evolution by natural selection. It is continued living both before and after the publication of Charles Darwin's 1859 book, ‘On the Origin of Species’. The whole human community is one species with the same genes. Mutation builds somewhat dissimilar translations of the similar genes, called alleles. Then meiosis and sexual reproduction combine different alleles in new ways to increase genetic variation. These little variations in the DNA series make each creature distinctive in its hair and skin color, dimension, form, figure, behavior and receptiveness of disease. These genetic dissimilarities are valuable in helping populations modify over time. Variations that help the living being go on to survive and to reproduce pass on to the subsequent
generations. The variations which obstruct the survival and the reproduction are abolished from that population. This progression of normal selection can lead to major changes in the form, appearance,
activities, behavior or functioning of the individuals in that population, in just a few subsequent generations.

To study genomic diversity polymorphic DNA Markers are widely used as most of them are selectively neutral, more ubiquitous than polymorphic protein and enzyme markers. Mitochondrial DNA (mtDNA) characterized high mutation rates caused by lack of protective histones, inefficient DNA repair systems and continuous exposure to mutagenic effects of oxygen radicals. In the present study PCR-RFLP techniques were used to reveal polymorphism of mtDNA D-loop region in Bhotia and Buxa tribes of Uttarakhand. The results showed 3 restriction patterns for HaeIII enzyme for Bhotia community and no restriction pattern for Alu I enzyme. In Bhotia and Buxa tribes of Uttarakhand ethnic prejudice is very high and kinship marriages greatly occurred between them. Furthermore, both the tribes lived in a close geographical area and have a little and limited communication with other parts of the country and these conditions confirmed the low level of heteroplasmy and polymorphic patterns for mtDNA D-loop region that observed in this population.

Introduction:  Sepsis is the systemic inflammatory response to
infection and remains primary cause of death from infection. Inflammatory markers and oxidative stress has a main role in the pathophysiology of sepsis.

Aims and objectives:  The present study aimed to assess oxidative stress markers (MDA, NO, Vitamin C, SOD, CAT), pro inflammatory markers (IL-6 & IL-8 and CRP) and anti-inflammatory marker (IL-10) in septic patients.

Methodology:  The study included 100 subjects which were divided into two groups. Group 1 (n=60) included ICU patients diagnosed with sepsis. Group 2 (n= 40) Healthy volunteers. Blood Samples were collected from healthy individuals and from septic patients. The oxidative stress markers (MDA, NO, SOD, CAT and Vitamin C levels were measured by spectrophotometer. IL-6, IL-8 were estimated by ELISA and CRP by Quantitative Turbidimetric Latex Assay Method.

Results: The mean serum levels of pro inflammatory cytokines (IL-6, IL-8, CRP) and anti-inflammatory IL- 10 septic patients were highly significantly increased
in septic patients as compared to control subjects. We found mean serum oxidative stress markers (MDA, NO, SOD and CAT) levels were significantly increased in septic patients as compared to control subjects. Mean serum Vitamin C levels were significantly decreased in septic patients as compared to control subjects (p<0.05)

Conclusion: Our study suggests infection and inflammation in septic patients leads to the production of pro inflammatory cytokines, ROS and RNS. This lead to imbalance in the inflammatory network and initiates oxidative stress induced lipid peroxidation of membrane lipids, which is mainly responsible for cellular or organs injury that’s confirmed by elevated
levels of SOD and CAT. Therefore these pro and antiinflammatory and oxidative stress markers are definitely used as a marker for SIRS and to assess progression and severity of the sepsis.