Key result
The combined LRP8 QQ and APOE E4 carrier genotype was associated with a significantly increased risk of myocardial infarction (OR 3.88) compared to the RR/non-E4 carrier genotype.
Why the study?
Does the combination of LRP8 R952Q variant and APOE ε2/ε3/ε4 genotype increase the risk of myocardial infarction and modulate ApoE levels in an Italian cohort?
Case-Control (n=681)
No
Does the combination of LRP8 R952Q variant and APOE ε2/ε3/ε4 genotype increase the risk of myocardial infarction and modulate ApoE levels in an Italian cohort?
Odds Ratio: 3.88 (95% CI 1.08–13.9)
p-value: p=0.007 for linear trend
The LRP8 R952Q variant has an additive effect to the APOE ε2/ε3/ε4 genotype in determining ApoE concentrations and increasing the risk of myocardial infarction.
Should not alter MI risk assessment; leaves open additive LRP8-APOE effects pending prospective validation.
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.
No takes yet. Share an insight, caveat, or question.
Martinelli et al. (2009) conducted a case-control in Myocardial infarction (n=681). Combined LRP8 R952Q (QQ) and APOE ε2/ε3/ε4 (E4 carrier) genotypes vs. LRP8 RR and non-carriers of APOE E4 was evaluated on Myocardial infarction (OR 3.88, 95% CI 1.08-13.9, p=0.007 for linear trend). The combined LRP8 QQ and APOE E4 carrier genotype was associated with a significantly increased risk of myocardial infarction (OR 3.88) compared to the RR/non-E4 carrier genotype.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: