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.
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).


CONCLUSIONS
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.
Martinelli
Nicola
N
Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy. nicola.martinelli@univr.it
Olivieri
Oliviero
O
Shen
Gong-Qing
GQ
Trabetti
Elisabetta
E
Pizzolo
Francesca
F
Busti
Fabiana
F
Friso
Simonetta
S
Bassi
Antonella
A
Li
Lin
L
Hu
Ying
Y
Pignatti
Pier Franco
PF
Corrocher
Roberto
R
Wang
Qing Kenneth
QK
Girelli
Domenico
D
D000368:Aged; D053329:Apolipoprotein E2 / Q000097:blood / Q000235:genetics*; D053318:Apolipoprotein E3 / Q000097:blood / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007558:Italy; D026502:LDL-Receptor Related Proteins; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D018110:Receptors, Lipoprotein / Q000235:genetics*; D012307:Risk Factors
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D026502:LDL-Receptor Related Proteins; D018110:Receptors, Lipoprotein; C098773:low density lipoprotein receptor-related protein 8