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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.
BMC Med Genet. 2009 May 13; 10:41.BM

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+Show Affiliations

Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy. nicola.martinelli@univr.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19439088

Citation

Martinelli, Nicola, et al. "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." BMC Medical Genetics, vol. 10, 2009, p. 41.
Martinelli N, Olivieri O, Shen GQ, et al. 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. BMC Med Genet. 2009;10:41.
Martinelli, N., Olivieri, O., Shen, G. Q., Trabetti, E., Pizzolo, F., Busti, F., Friso, S., Bassi, A., Li, L., Hu, Y., Pignatti, P. F., Corrocher, R., Wang, Q. K., & Girelli, D. (2009). 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. BMC Medical Genetics, 10, 41. https://doi.org/10.1186/1471-2350-10-41
Martinelli N, et al. 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. BMC Med Genet. 2009 May 13;10:41. PubMed PMID: 19439088.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Martinelli,Nicola, AU - Olivieri,Oliviero, AU - Shen,Gong-Qing, AU - Trabetti,Elisabetta, AU - Pizzolo,Francesca, AU - Busti,Fabiana, AU - Friso,Simonetta, AU - Bassi,Antonella, AU - Li,Lin, AU - Hu,Ying, AU - Pignatti,Pier Franco, AU - Corrocher,Roberto, AU - Wang,Qing Kenneth, AU - Girelli,Domenico, Y1 - 2009/05/13/ PY - 2008/11/12/received PY - 2009/05/13/accepted PY - 2009/5/15/entrez PY - 2009/5/15/pubmed PY - 2009/6/9/medline SP - 41 EP - 41 JF - BMC medical genetics JO - BMC Med Genet VL - 10 N2 - 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. SN - 1471-2350 UR - https://www.unboundmedicine.com/medline/citation/19439088/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_ L2 - https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-10-41 DB - PRIME DP - Unbound Medicine ER -