Matrix metalloproteinase 3 haplotypes and plasma amyloid beta levels: The Rotterdam Study

Experimental studies suggest that matrix metalloproteinases (MMPs) are involved in the degradation of amyloid beta (A beta) protein which plays a key role in the pathogenesis of Alzheimer's disease Whether MMPs are associated with changes in beta amyloid levels in humans remains unclear We related common haplotypes within the gene encoding MMP-3 with plasma levels of A beta(1-10) and A beta(1-12) in 1621 non-demented participants of the population-based Rotterdam Study In non-demented persons. plasma A beta concentration reflect levels of A beta in the brain DNA was genotyped for polymorphisms 1187 (5A6A, rs3025058), 2092A>G (rs522616). 9775T>A (rs563096) and 6658T>C (rs3025066) and haplotypes reconstructed (coding from 1187 (5A6A), 2092A>G. 9775-1>A and 6658T>C haplotype 1 = 5A-A-T-T. haplotype 2 = 6A-G-T-T, haplotype 3 = 6A-A-T-T. haplotype 4 = 6A-A-A-T and haplotype 5 = 5A-A-T-C) Then the associations of these haplotypes with plasma A beta(1-10) and A beta(1-42) levels were assessed using the program Stats Compared with haplotype I. haplotype 4 was associated with significantly lower levels of plasma A beta(1-40) (beta=8 04. 95% CI (-14 79 -1 28), p =0 02) after adjusting for age and sex Haplotype 2 was associated with significantly higher levels of plasma A beta(1-42) (beta=3 70,95% CI (1 75.5 65),p = 0 0002) Our observations suggest that variation in the gene encoding MMP-3 is associated with changes in amyloid beta levels in humans Factors modulating secretion or activity of MMP-3 may have the potential to in the amount of An concentration and deposition in the brain (C) 2008 Elsevier Inc. All rights reserved