Genetic variants of <I>ABCA1</I> modify Alzheimer disease risk and quantitative traits related to &bgr;-amyloid metabolism Export

@article{citeulike:1069805, abstract = {Linkage studies have provided evidence that one or more loci on chromosome 9q influence Alzheimer disease (AD). The gene encoding the ATP-binding cassette A1 transporter (ABCA1) resides within proximity of previously identified linkage peaks and represents a plausible biological candidate for AD due to its central role in cellular lipid homeostasis. Several single nucleotide polymorphisms (SNPs) spanning ABCA1 have been genotyped and haplotype-based association analyses performed in four independent case-control samples, consisting of over 1,750 individuals from three European populations representing both early and late-onset AD. Prominent effects were observed for a common (H2) and rarer haplotype (H5) that were enriched in AD cases across studied populations (odds ratio [OR] 1.59, 95\% confidence interval [CI] 1.36-1.82; P\&lt;0.00001 and OR 2.90; 95\% CI 2.54-3.27; P\&lt;0.00001, respectively). Two other common haplotypes in the studied region (H1 and H3) were significantly under-represented in AD cases, suggesting that they may harbor alleles that decrease disease risk (OR 0.79, 95\% CI 0.64-0.94; P=0.0065 and OR 0.70, 95\% CI 0.46-0.93; P=0.011, respectively). While findings were significant in both early and late-onset samples, haplotype effects were more distinct in early-onset materials. For late-onset samples, ancillary evidence was obtained that both single marker alleles and haplotypes of ABCA1 contribute to variable cerebrospinal fluid tau and beta amyloid (A\&bgr;42) protein levels, and brain A\&bgr; load. Results indicate that variants of ABCA1 may affect the risk of AD, providing further support for a genetic link between AD and cholesterol metabolism. Hum Mutat 23:358-367, 2004 {\copyright} 2004 Wiley-Liss, Inc.}, address = {Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, Sweden; Department of Care of the Elderly, University of Bristol, Frenchay Hospital, Bristol, UK; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Mathematical Statistics, Stockholm University, Stockholm, Sweden; Neurotec, Department of Geriatric Medicine, Huddinge University Hospital, Stockholm, Sweden; Department of Psychology, University of G\"{o}teborg, G\"{o}teborg, Sweden; Department of Neuropathology, Institute of Psychiatry, King's College, London, UK; Department of Psychology, University of Southern California, Los Angeles, CA; Department of Clinical Neuroscience and Transfusion Medicine, University of G\"{o}teborg, Sahlgren's University Hospital, G\"{o}teborg, Sweden}, author = {Katzov, Hagit and Chalmers, Katy and Palmgren, Juni and Andreasen, Niels and Johansson, Boo and Cairns, Nigel J. and Gatz, Margaret and Wilcock, Gordon K. and Love, Seth and Pedersen, Nancy L. and Brookes, Anthony J. and Blennow, Kaj and Kehoe, Patrick G. and Prince, Jonathan A.}, citeulike-article-id = {1069805}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/humu.20012}, citeulike-linkout-1 = {http://www3.interscience.wiley.com/cgi-bin/abstract/107632452/ABSTRACT}, doi = {10.1002/humu.20012}, journal = {Human Mutation}, keywords = {aggregation, disease-associated, snps}, number = {4}, pages = {358--367}, posted-at = {2007-01-26 20:35:40}, priority = {2}, title = {Genetic variants of <I>ABCA1</I> modify Alzheimer disease risk and quantitative traits related to \&bgr;-amyloid metabolism}, url = {http://dx.doi.org/10.1002/humu.20012}, volume = {23}, year = {2004} }

TY - JOUR ID - citeulike:1069805 L3 - citeulike-article-id:1069805 N2 - Linkage studies have provided evidence that one or more loci on chromosome 9q influence Alzheimer disease (AD). The gene encoding the ATP-binding cassette A1 transporter (ABCA1) resides within proximity of previously identified linkage peaks and represents a plausible biological candidate for AD due to its central role in cellular lipid homeostasis. Several single nucleotide polymorphisms (SNPs) spanning ABCA1 have been genotyped and haplotype-based association analyses performed in four independent case-control samples, consisting of over 1,750 individuals from three European populations representing both early and late-onset AD. Prominent effects were observed for a common (H2) and rarer haplotype (H5) that were enriched in AD cases across studied populations (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.36-1.82; P&lt;0.00001 and OR 2.90; 95% CI 2.54-3.27; P&lt;0.00001, respectively). Two other common haplotypes in the studied region (H1 and H3) were significantly under-represented in AD cases, suggesting that they may harbor alleles that decrease disease risk (OR 0.79, 95% CI 0.64-0.94; P=0.0065 and OR 0.70, 95% CI 0.46-0.93; P=0.011, respectively). While findings were significant in both early and late-onset samples, haplotype effects were more distinct in early-onset materials. For late-onset samples, ancillary evidence was obtained that both single marker alleles and haplotypes of ABCA1 contribute to variable cerebrospinal fluid tau and beta amyloid (A&bgr;42) protein levels, and brain A&bgr; load. Results indicate that variants of ABCA1 may affect the risk of AD, providing further support for a genetic link between AD and cholesterol metabolism. Hum Mutat 23:358-367, 2004 © 2004 Wiley-Liss, Inc. IS - 4 JF - Human Mutation AD - Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, Sweden; Department of Care of the Elderly, University of Bristol, Frenchay Hospital, Bristol, UK; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Mathematical Statistics, Stockholm University, Stockholm, Sweden; Neurotec, Department of Geriatric Medicine, Huddinge University Hospital, Stockholm, Sweden; Department of Psychology, University of Göteborg, Göteborg, Sweden; Department of Neuropathology, Institute of Psychiatry, King's College, London, UK; Department of Psychology, University of Southern California, Los Angeles, CA; Department of Clinical Neuroscience and Transfusion Medicine, University of Göteborg, Sahlgren's University Hospital, Göteborg, Sweden EP - 367 TI - Genetic variants of <I>ABCA1</I> modify Alzheimer disease risk and quantitative traits related to &bgr;-amyloid metabolism VL - 23 SP - 358 KW - aggregation KW - disease-associated KW - snps AU - Katzov, Hagit AU - Chalmers, Katy AU - Palmgren, Juni AU - Andreasen, Niels AU - Johansson, Boo AU - Cairns, Nigel AU - Gatz, Margaret AU - Wilcock, Gordon AU - Love, Seth AU - Pedersen, Nancy AU - Brookes, Anthony AU - Blennow, Kaj AU - Kehoe, Patrick AU - Prince, Jonathan PY - 2004/// UR - http://dx.doi.org/10.1002/humu.20012 ER -