SORL1 haplotypes modulate risk of Alzheimer's disease in Chinese

• Published in: Neurobiology of aging 2009-07, Vol.30 (7), p.1048-1051
• Main Authors: Tan, E.K, Lee, J, Chen, C.P, Teo, Y.Y, Zhao, Y, Lee, W.L
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer's disease; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Brain Chemistry - genetics; Chinese; Continental Population Groups - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; DNA Mutational Analysis; Female; Fundamental and applied biological sciences. Psychology; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; Genetic Testing; Genotype; Haplotype; Haplotypes - genetics; Humans; Internal Medicine; LDL-Receptor Related Proteins - genetics; Male; Medical sciences; Membrane Transport Proteins - genetics; Middle Aged; Multigene Family - genetics; Neurology; Polymorphism, Single Nucleotide - genetics; Risk Factors; Singapore; SORL1; Vertebrates: nervous system and sense organs
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2007.10.013

Abstract Genetic variants of the neuronal sortilin - related receptor ( SORL1 ) have been demonstrated to modulate the risk of Alzheimer's disease (AD) in different American and European populations [Rogaeva, E., Meng, Y., Lee, J.H., Gu, Y., Kawarai, T., Zou, F., Katayama, T., Baldwin, C.T., Cheng, R., Hasegawa, H., Chen, F., Shibata, N., Lunetta, K.L., Pardossi-Piquard, R., Bohm, C., Wakutani, Y., Cupples, L.A., Cuenco, K.T., Green, R.C., Pinessi, L., Rainero, I., Sorbi, S., Bruni, A., Duara, R., Friedland, R.P., Inzelberg, R., Hampe, W., Bujo, H., Song, Y.Q., Andersen, O.M., Willnow, T.E., Graff-Radford, N., Petersen, R.C., Dickson, D., Der, S.D., Fraser, P.E., Schmitt-Ulms, G., Younkin, S., Mayeux, R., Farrer, L.A., St George-Hyslop, P., 2007. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat. Genet. 39 (2), 168–177]. We conducted haloptype analysis involving two genetic clusters of SORL1 in AD and controls among Han Chinese. rs3824968 (SNP 23) was associated with an increased risk of AD, and there was a trend towards association for rs1699102 (SNP 22) and rs2282649 (SNP 24). More robust associations were found for three-loci haplotypes. In particular, the GCA haplotype at SNPs 19–22–23 was associated with an increased risk (odds ratio 1.4), and CTC haplotype at SNPs 19–22–23 and TCT at SNPs 22–23–24 a decreased risk (odds ratio 0.67) of AD. The complete absence of some at-risk North European haplotypes in our Chinese study subjects was likely due to different ancestral origins, with allelic heterogeneity among races. However, our study suggests that certain SORL1 haplotypes at SNPs 19–24 modulated risk of AD in our Chinese population.