We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Additive effect of LRP8/APOER2 R952Q variant to APOE ε2/ε3/ε4 genotype in modulating apolipoprotein E concentration and the risk of myocardial infarction: a case-control study.
- Authors
Martinelli, Nicola; Olivieri, Oliviero; Gong-Qing Shen; Trabetti, Elisabetta; Pizzolo, Francesca; Busti, Fabiana; Friso, Simonetta; Bassi, Antonella; Lin Li; Ying Hu; Pignatti, Pier Franco; Corrocher, Roberto; Qing Kenneth Wang; Girelli, Domenico
- 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) ε2/ε3/ε4 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 ε2/ε3/ε4 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 ε2/ ε3/ε4 genotype in determining ApoE concentrations and risk of MI in an Italian population.
- Subjects
LOW density lipoproteins; APOLIPOPROTEIN E; MYOCARDIAL infarction; ITALIANS; POPULATION genetics
- Publication
BMC Medical Genetics, 2009, Vol 10, p1
- ISSN
1471-2350
- Publication type
Article
- DOI
10.1186/1471-2350-10-41