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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

González, Pelayoa; Álvarez, Rutha; Reguero, Julián R.b; Batalla, Albertoc; Álvarez, Victoriaa; Cortina, Arturob; Cubero, Gustavo I.b; García-Castro, Mónicaa; Coto, Eliecera

Pathophysiology and Natural History

Background The 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.

Objective To evaluate the association between DNA polymorphisms at the LRP, LRPAP and α2 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 α2 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.

aLaboratorio de Genética Molecular-Instituto de Investigación Nefrológica (IRSIN-FRIAT)

bServicio de Cardiología, Hospital Central Asturias, Oviedo

cServicio de Cardiología, Hospital Cabueñes, Gijón, Spain

Sponsorship: This study was supported by Grants FIS 01/0356 and FICYT-MED01-03 to E.C. P.G. and R.A. were the recipients of fellowships from the Principado de Asturias-FICYT and the Spanish Fondo de Investigaciones Sanitarias. M.G.-C. was the recipient of a fellowship from Sociedad Asturiana de Cardiología.

Correspondence and requests for reprints to Eliecer Coto, Laboratorio de Genética Molecular, Hospital Central de Asturias, 33006, Oviedo, Spain.

Fax: +34 985 27 36 57; e-mail:

Received 19 March 2002 Revised 25 June 2002 Accepted 28 June 2002

© 2002 Lippincott Williams & Wilkins, Inc.