Variation in the lipoprotein receptor-related protein, alpha2-macroglobulin and lipoprotein receptor-associated protein genes in relation to plasma lipid levels and risk of early myocardial infarction

Coron Artery Dis. 2002 Aug;13(5):251-4. doi: 10.1097/00019501-200208000-00001.

Abstract

Background: The lipoprotein receptor-related protein (LRP) is an endocytic receptor for several ligands, such as alpha2-macroglobulin (alpha2 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.

Objective: To evaluate the association between DNA polymorphisms at the LRP, LRPAP and alpha2 M genes and early myocardial infarction (MI).

Methods: We genotyped 210 patients with early MI (<55 years) and 200 healthy control participants for three polymorphisms in the LRP, LRPAP and alpha2 M genes.

Results: No 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).

Conclusions: According to our data, the variation at the LRPAP1 gene could contribute to the risk of developing an early episode of MI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Humans
  • Introns / genetics
  • LDL-Receptor Related Protein-Associated Protein / genetics*
  • LDL-Receptor Related Proteins / genetics*
  • Male
  • Middle Aged
  • Myocardial Infarction / genetics*
  • Polymorphism, Genetic*
  • alpha-Macroglobulins / genetics*

Substances

  • LDL-Receptor Related Protein-Associated Protein
  • LDL-Receptor Related Proteins
  • alpha-Macroglobulins