Splice-site mutations and atherosclerosis: mechanisms and prediction models

Nucleotide variants in genes of the lipid metabolism influence the risk of premature atherosclerosis. Ten percent of all single nucleotide substitutio ns in these genes involve splice sites. The effects of these changes on mRN A splicing and phenotypic severity, however, are not inherently obvious fro m the nucleotide sequence. This review presents various genes of lipid metabolism with splicing mutati ons known to influence the risk of premature atherosclerosis. Mechanisms of pre-mRNA splicing are illustrated and different models for prediction of t he effect of nucleotide substitutions on splice-site function are presented . The role of information theory-based models is emphasized along with its role for prediction of splice-site function and phenotypic severity of athe rosclerosis.