In silico Analysis
of Non Synonymous Single Nucleotide Polymorphisms of Human LPA gene associated with
Ischemic Heart Disease
Kulkarni Vineet, Shetty Sukanya, Bhandary Roopa and Mary Yanglem
Res. J. Biotech.; Vol. 20(4); 184-190;
doi: https://doi.org/10.25303/204rjbt1840190; (2025)
Abstract
Ischemic heart disease (IHD) is a serious medical condition that has been linked
to higher levels of Lipoprotein (a) in the blood. However, the genetic factors that
lead to this increase in Lipoprotein (a) and the subsequent risk of IHD, are not
well understood. To shed more light on this issue, this study aims to use computational
methods to investigate the role of functional single nucleotide polymorphism(SNP)
in Lp(a)(LPA) gene expression.Functional SNPs for the LPA gene were retrieved from
the db SNP database. Two in silico tools, SIFT and SNAP 2, were used to identify
the most damaging SNPs in the LPA gene. The Mupro web tool was used to predict protein
stability changes resulting from single-site mutations in the APOA protein. The
web tool ConSurf was used to determine the evolutionary conservation analysis of
functional SNPs in LPA. The project HOPE software was used to predict protein structure
and to analyse the effects of the mutations.29 missense SNPs were selected for this
study using the SIFT database.
According to the MUPro Server, 27 SNPs were found to decrease protein stability
(G0.5). Among the 29 SNPs investigated, 6 were found to be average, 11 were conserved
and 8 were not conserved evolutionarily. According to HOPE analysis, all SNPs were
found to be damaging which could alter the properties of amino acids in different
Kringle regions. This study provides evidence that polymorphism in the LPA gene
can impact its cellular function and serum Lp(a) level.
