In Silica Analysis Of Single Nucleotide Polymorphisms Of Leptin And Leptin Receptor Gene : A Preliminary Bioinformatics Data

Abstract

Introduction: Depression and obesity are two common disorders that regularly co-occur in people and have substantial public health repercussions. Both conditions are linked in a bidirectional way: having one increases the chances of obtaining the other. Leptin is the adipokine hormone that has a role in obesity as well as known to influence the mood. Mutations of leptin and its receptor genes have been least studied in both the conditions. The aim of the study is to carry out the in silica analysis of leptin and its receptor gene using bioinformatics tools to predict the functional effects of the non-synonymous SNPs of these genes.
Method: Insilico analysis of SNPs of leptin and its receptor gene were carried out using their accession IDs and their FASTA amino acid sequences obtained from NCBI. SIFT(Sorting the intolerant from tolerant), Provean (protein variation effect analyzer) and I mutant 3.0 were the bioinformatics tools used for the analysis.
Results: Analysis ofSNPs ofleptin gene by SIFT revealed 75% tolerated and 25% damaging mutations. Provean analysis showed 31% deleterious and 69% neutral mutations. On I mutant analysis,85% of the SNPs resulted in decreased thermodynamic stability whereas 15% of them had increased stability. 69% of SNPs of leptin receptor genes were found to be damaging on SIFT,18% on Provean and 94.4% of them showed decreased stability.
Conclusion: The study suggests strongly that deleterious effects of mutations on leptin and its receptor as well as their reduced stability predicted by the bioinformatics toolsaffect their structure and function. Mutations of leptin receptor may be more deleterious compared to that of leptin gene.These mutations may influence the pathobiology of depression as well asobesityand wet lab study on these genes may be useful in linking the pathogenesis of obesity and depression.