Association of SORL1 gene variants with Alzheimer's disease

• Published in: Brain research 2009-04, Vol.1264, p.1-6
• Main Authors: Kölsch, Heike, Jessen, Frank, Wiltfang, Jens, Lewczuk, Piotr, Dichgans, Martin, Teipel, Stefan J, Kornhuber, Johannes, Frölich, Lutz, Heuser, Isabella, Peters, Oliver, Wiese, Birgitt, Kaduszkiewicz, Hanna, van den Bussche, Hendrik, Hüll, Michael, Kurz, Alexander, Rüther, Eckhart, Henn, Fritz A, Maier, Wolfgang
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Age at onset; Age of Onset; Aged; Alleles; Alzheimer dementia; Alzheimer Disease - genetics; Association; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Gene Frequency; Genetic Predisposition to Disease - genetics; Genetic Variation; Haplotypes; Humans; Kaplan-Meier Estimate; LDL-Receptor Related Proteins - genetics; Male; Medical sciences; Membrane Transport Proteins - genetics; Neurology; Organic mental disorders. Neuropsychology; Polymorphism, Genetic - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Regression Analysis; SORL1
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.01.044

Abstract SORL1 gene variants were described as risk factor of Alzheimer's disease (AD) additionally SORL1 gene variants were associated with altered Aβ42 CSF levels in AD patients. In the present study we investigated the association of SORL1 gene variants (rs2070045 (SNP19), SORL1-18ex26 (SNP21), rs3824968 (SNP23), rs1010159 (SNP25)) with AD risk by using Cox proportional hazard model and Kaplan–Meier survival analysis in 349 AD patients and 483 controls, recruited from a multicenter study of the German Competence Network Dementias. The SNP21G-allele and a SORL1 haplotype consisting of the SNP19 T-allele, SNP21 G-allele and SNP23 A-allele (T/G/A) were associated with increased hazard ratios and an earlier age at onset of AD (SNP21: p = 0.002; T/G/A haplotype: p = 0.007). This effect was most pronounced in carriers of an additional APOE4 allele (SNP21: p = 0.003; T/G/A haplotype: p = 0.005). In conclusion, we found SORL1 gene variants located in the 3′ region of the gene to be associated with increased AD risk and an earlier age at onset of AD in our Central-European population. Thus, our data support a role of SORL1 polymorphisms in AD.