Biyoinformatik araçlar aracılığıyla insan APOE (Apolipoprotein E) genindeki yanlış anlamlı SNV'lerin değerlendirilmesi

Abstract

Apolipoprotein E (APOE) is one of the main proteins responsible for cholesterol transport. It has three major isoforms, APOE2, APOE3, and APOE4. The purpose of this study is to investigate the possible effects of single nucleotide variations (SNVs) in the APOE gene, which cause amino acid substitution, on the function, structure and stabilization of the APOE protein using bioinformatics/s tools. SNVs and protein sequence information were obtained from NCBI and UniProt databases. Bioinformatical analysis was performed using a series of tools such as SIFT, PolyPhen-2, SNPs&GO, Mutation Assessor, PROVEAN, SNAP2, I-Mutant-3, MUPro, and Project HOPE. As a result, 321 missense SNVs were analyzed and rs7412 (R176C), rs769455 (R163C), rs11542029 (R50C), rs121918393 (R154S), rs121918394 (K164Q), rs200703101 (R154P), rs387906567 (R160C), rs11542040 (P102T), rs11542041 (R132S) and rs41382345 (E139V) were predicted to be deleterious/disease related after functional analysis and pathological effect analysis via all of the bioinformatics/s tools. According to the protein stabilization results, it was determined that all SNVs decreased protein stabilization with the MUPro software tool, and two SNVs (rs121918394, rs41382345) increased protein stabilization with the I-Mutant-3 software tool. The models of protein and amino acid properties were obtained via Project HOPE for all high-risk SNVs. We hope our analysis will be valuable for further proteomic, genomic, and clinical research.