title: Common polymorphisms in LRP and A2M do not affect genetic risk for Alzheimer disease in Northern Ireland.
abstract: Genetic variation in one of the major APOE receptors in the brain has been associated with increased risk for Alzheimer disease (AD). A C/T polymorphism in exon 3 and a tetranucleotide repeat polymorphism in the 5' region of the low-density lipoprotein receptor-related protein gene have been reported to increase risk in some studies but these reports have not been universally replicated. In addition, genetic variation in another ligand of LRP, alpha-2 macroglobulin (A2M), has also been associated with increased AD risk. However, these reports also remain controversial. We have genotyped both LRP polymorphisms and two polymorphisms in the A2M gene in a large group of clinically well-defined AD cases and controls from the relatively genetically homogeneous Northern Ireland population. Comparison of genotype and allele frequencies for polymorphisms in LRP revealed no significant differences between cases and controls. Multiple logistic regression analysis performed to assess any possible interaction between LRP and APOE revealed little evidence for genetic interaction despite the obvious biological interaction. Genotype and allele comparisons between the groups for the A2M polymorphisms also gave no evidence that either polymorphism increased risk for disease. The results from this study indicate that polymorphisms in LRP and A2M are not associated with increased risk for AD in Northern Ireland.
authors.affiliation: Department of Geriatric Medicine, The Queen's University of Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland. m.mcilroy@qub.ac.uk
authors.forename: S P
authors.initials: SP
authors.lastname: McIlroy
authors.forename: K B
authors.initials: KB
authors.lastname: Dynan
authors.forename: D J
authors.initials: DJ
authors.lastname: Vahidassr
authors.forename: J T
authors.initials: JT
authors.lastname: Lawson
authors.forename: C C
authors.initials: CC
authors.lastname: Patterson
authors.forename: P
authors.initials: P
authors.lastname: Passmore
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009660:Northern Ireland; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000235:genetics*; D012307:Risk Factors; D000511:alpha-Macroglobulins / Q000235:genetics*
chemical_list: D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; D004247:DNA