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.
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.
González
Pelayo
P
Laboratorio de Genética Molecular-Instituto de Investigación Nefrológica (IRSIN-FRIAT), Hospital Central Asturias, Oviedo, Spain.
Alvarez
Ruth
R
Reguero
Julián R
JR
Batalla
Alberto
A
Alvarez
Victoria
V
Cortina
Arturo
A
Cubero
Gustavo I
GI
García-Castro
Mónica
M
Coto
Eliecer
E
D000328:Adult; D006801:Humans; D007438:Introns / Q000235:genetics; D026563:LDL-Receptor Related Protein-Associated Protein / Q000235:genetics*; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic; D000511:alpha-Macroglobulins / Q000235:genetics*
D026563:LDL-Receptor Related Protein-Associated Protein; D026502:LDL-Receptor Related Proteins; D000511:alpha-Macroglobulins