Abstract
Plasma concentrations of Aβ40 and Aβ42 rise with age and are increased in people with mutations that cause early-onset Alzheimer's disease (AD). Amyloid beta (Aβ) plasma levels were successfully used as an (endo)phenotype for gene discovery using a linkage approach in families with dominant forms of disease. Here, we searched for loci involved in Aβ plasma levels in a series of non-demented patients with hypertension in the Erasmus Rucphen Family study. Aβ40 and Aβ42 levels were determined in 125 subjects with severe hypertension. All patients were genotyped with a 6,000 single nucleotide polymorphisms (SNPs) illumina array designed for linkage analysis. We conducted linkage analysis of plasma Aβ levels. None of the linkage analyses yielded genome-wide significant logarithm of odds (LOD) score over 3.3, but there was suggestive evidence for linkage (LOD > 1.9) for two regions: 1q41 (LOD = 2.07) and 11q14.3 (LOD = 2.97), both for Aβ40. These regions were followed up with association analysis in the study subjects and in 320 subjects from a population-based cohort. For the Aβ40 region on chromosome 1, association of several SNPs was observed at the presenilin 2 gene (PSEN2) (p = 2.58 × 10(-4) for rs6703170). On chromosome 11q14-21, we found some association (p = 3.1 × 10(-3) for rs2514299). This linkage study of plasma concentrations of Aβ40 and Aβ42 yielded two suggestive regions, of which one points toward a known locus for familial AD.
Original language | English |
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Pages (from-to) | 1869-76 |
Number of pages | 8 |
Journal | Human Genetics |
Volume | 131 |
Issue number | 12 |
DOIs | |
Publication status | Published - Dec 2012 |
Externally published | Yes |
Keywords
- Aged
- Alzheimer Disease/genetics
- Amyloid beta-Peptides/blood
- Chromosomes, Human, Pair 1/genetics
- Chromosomes, Human, Pair 11/genetics
- Cohort Studies
- Female
- Genetic Linkage
- Genetic Predisposition to Disease
- Humans
- Hypertension/blood
- Lod Score
- Male
- Middle Aged
- Netherlands
- Peptide Fragments/blood
- Polymorphism, Single Nucleotide
- Presenilin-2/genetics