Additive effect of LRP8/APOER2 R952Q variant to APOE epsilon2/epsilon3/epsilon4 genotype in modulating apolipoprotein E concentration and the risk of myocardial infarction: a case-control study.

Abstract

BACKGROUND:

The R952Q variant in the low density lipoprotein receptor-related protein 8 (LRP8)/apolipoprotein E receptor 2 (ApoER2) gene has been recently associated with familial and premature myocardial infarction (MI) by means of genome-wide linkage scan/association studies. We were interested in the possible interaction of the R952Q variant with another established cardiovascular genetic risk factor belonging to the same pathway, namely apolipoprotein E (APOE) epsilon2/epsilon3/epsilon4 genotype, in modulating apolipoprotein E (ApoE) plasma levels and risk of MI.

METHODS:

In the Italian cohort used to confirm the association of the R952Q variant with MI, we assessed lipid profile, apolipoprotein concentrations, and APOE epsilon2/epsilon3/epsilon4 genotype. Complete data were available for a total of 681 subjects in a case-control setting (287 controls and 394 patients with MI).

RESULTS:

Plasma ApoE levels decreased progressively across R952Q genotypes (mean levels +/- SD = RR: 0.045 +/- 0.020, RQ: 0.044 +/- 0.014, QQ: 0.040 +/- 0.008 g/l; P for trend = 0.047). Combination with APOE genotypes revealed an additive effect on ApoE levels, with the highest level observed in RR/non-carriers of the E4 allele (0.046 +/- 0.021 g/l), and the lowest level in QQ/E4 carriers (0.035 +/- 0.009 g/l; P for trend = 0.010). QQ/E4 was also the combined genotype with the most significant association with MI (OR 3.88 with 95%CI 1.08-13.9 as compared with RR/non-carriers E4).

CONCLUSION:

Our data suggest that LRP8 R952Q variant may have an additive effect to APOE epsilon2/epsilon3/epsilon4 genotype in determining ApoE concentrations and risk of MI in an Italian population.

• Authors: Nicola Martinelli, Oliviero Olivieri, Gong-Qing Shen, Elisabetta Trabetti, Francesca Pizzolo, Fabiana Busti, Simonetta Friso, Antonella Bassi, Lin Li, Ying Hu, Pier Franco Pignatti, Roberto Corrocher, Qing Kenneth Wang, Domenico Girelli
• Journal: BMC medical genetics (BMC Med Genet) Vol. 10 Pg. 41 (May 13 2009) ISSN: 1471-2350 [Electronic] England
• PMID: 19439088 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein E2
• Apolipoprotein E3
• Apolipoprotein E4
• LDL-Receptor Related Proteins
• Receptors, Lipoprotein
• low density lipoprotein receptor-related protein 8

Topics

• Aged
• Apolipoprotein E2 (blood, genetics)
• Apolipoprotein E3 (blood, genetics)
• Apolipoprotein E4 (blood, genetics)
• Case-Control Studies
• Cohort Studies
• Female
• Genetic Predisposition to Disease
• Genetic Variation
• Genome-Wide Association Study
• Genotype
• Humans
• Italy
• LDL-Receptor Related Proteins
• Male
• Middle Aged
• Myocardial Infarction (blood, genetics)
• Receptors, Lipoprotein (genetics)
• Risk Factors