Mining the SNPs of Human Low Density Lipoprotein (LDL) related Gene APOB through in silico Approaches
Mining the SNPs of Human Low Density Lipoprotein (LDL) related Gene APOB through in silico Approaches
Muneeza Zafar1,2,3, Fazli Rabbi Awan2,*, Munazza Raza Mirza3,*, Sumaira Nishat2,4, Sajid Ali Rajput5 and Imran Riaz Malik1,*
ABSTRACT
Apolipoprotein B (APOB) is the major part of low density lipoprotein (LDL), with two major isoforms: APOB100 and APOB48 found in the human body. Both isoforms are involved in the formation and transport of chylomicron and LDL-cholesterol. Point mutations in APOB may lead to change in protein stereochemistry, which may result in premature coronary artery disease, familial hypobetalipoproteinemia, hypocholesterolemia, mono-genic dyslipisimias and other atherogenic events in CVD. Here we evaluated the impact of all missense and non-coding single nucleotide polymorphisms (SNPs) of APOB retrieved from dbSNP using 17 different computational tools and further evaluated the structural impact of these convergent deleterious SNPs on APOB through HOPE. We found 9 missenses, 15 intronic or regulatory region SNPs and 2 were found in miRNA target sites of APOB. Out of these variant, the rs13306194 (Arg532Trp) was found in the conserved region of protein domain, which can potentially disrupt overall chemical structure and function of the APOB. Six missense SNPs in the coding, and 17 SNPs in non-coding regions are proposed as novel most deleterious variants of APOB. We also try to predict the structural model of APOB through protein docking. The results indicate the applicability of in silico approach to propose the most deleterious SNPs of APOB that should be prioritize for future genetic association studies in cohort of cardiovascular patients. While their structural impact on APOB may suggest these predicted nsSNPs possibly be a better drug target and contribute to the treatment and better understanding of human cardiovascular disease.
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