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Variation in the lipoprotein receptor-related protein, α2-macroglobulin and lipoprotein receptor-associatedprotein genes in relation to plasma lipid levels and riskof early myocardial infarction

BackgroundThe lipoprotein receptor-related protein (LRP) is an endocytic receptor for several ligands, such as α2-macroglobulin (α2 M) and apolipoprotein E. LRP is involved in the clearance of lipids from the bloodstream and is expressed in the atherosclerotic plaque. The LRP-associated protein (LRPAP in humans, RAP in mice) acts as a chaperone protein, stabilizing the nascent LRP peptide in the endoplasmic reticulum and Golgi complex. In mice, the amount of LRP activity was modulated by RAP, and RAP-null mice showed higher levels of total cholesterol. ObjectiveTo evaluate the association between DNA polymorphisms at the LRP, LRPAP and α2 M genes and early myocardial infarction (MI). MethodsWe genotyped 210 patients with early MI (<55 years) and 200 healthy control participants for three polymorphisms in the LRP, LRPAP and α2 M genes. ResultsNo association was found between these polymorphisms and plasma lipid levels in patients and control participants. Only the LRPAP-intron 1 polymorphism (a 21 bp insertion/deletion) was associated with MI (P = 0.0065; odds ratio = 2.18, 95% confidence intervals = 1.22–3.90). ConclusionsAccording to our data, the variation at the LRPAP1 gene could contribute to the risk of developing an early episode of MI.