Computational analysis to identify deleterious nsSNPs and its impact on IL 6 protein in inflammation

Abstract

IL 6 is a pro-inflammatory cytokine involved in driving inflammation and the acute phase immune response. Hence, it is important to predict SNPs which could affect IL-6 stability and thus inflammatory conditions. Therefore, this study was undertaken to find the functional nsSNPs in IL 6. Out of total 243 SNPs, 37 were nsSNPs (non-synonymous), 7 occurred in the mRNA 3’UTR, 7 occurred in 5’ UTR region, 193 occurred in intronic regions and rest were other types of SNPs. Among the predicted nsSNPs, rs2069860, rs11544633 were identified as deleterious and damaging by different programs. Additionally, I-Mutant showed a decrease in stability for these nsSNPs upon mutation. Protein structural analysis with these amino acid variants was performed by using I-Mutant and Swiss PDB viewer to check their molecular dynamics and energy minimization calculations. We also identified several IL 6 sites that may undergo post-translational modification, including sites that coincide with the location of high-risk nsSNPs. This study suggested that D162V and P119L variants of IL 6 could directly or indirectly destabilize the amino acid interactions and could be useful for evaluation of genotype association study with inflammatory diseases.