Lack of interaction between LRP1 and A2M polymorphisms for the risk of Alzheimer disease

Alzheimer disease (AD) has a heterogeneous aetiology, involving genetic and environmental factors. Low-density lipoprotein receptor-related protein 1 (LRP1), alpha-2-macroglobulin (A2M) and apolipoprotein E (APOE) are involved in molecular pathways leading to beta-amyloid deposition. Three polymorphic sites in these genes (APOE-epsilon 2/epsilon 3/epsilon 4, A2M-Ile/Val and LRP1-C/T) have been associated with AD, but the results were not univocal. We carried out a case-control study to investigate the association between these polymorphisms and the risk of developing AD and their possible interaction. We recruited 125 AD patients who fulfilled the diagnostic criteria proposed by NINCDS-ADRDA for probable or possible AD and 310 controls subjects. PCR was used to detect the polymorphisms. ORs and 95% CIs were estimated using logistic regression analysis. The OR for subjects carrying at least one allele Val (A2M-Val+) in their genotypes was 1.52 (95% CI 1.00-2.31; p=0.05); for subjects carrying at least one allele C (LRP1-C+), 1.58 (95% CI 1.00-2.50; p=0.05); for subjects carrying at least one allele epsilon 4 (APOE-epsilon 4+), 3.1 (95%CI 1.87-5.00; p<0.001). The coexistence of at least one allele Val (A2M-Val+) and one allele C (LRP1-C+) increased up two times the risk of AD (OR 2.32; 95% CI 1.23-4.35; p<0.009). No evidence of significant interaction has been found between the studied polymorphisms (p>0.05). In conclusion our study suggests that LRP1-C/T, A2M-Ile/Val and APOE-epsilon 2/epsilon 3/epsilon 4 polymorphisms are associated with AD.