Association of SORL1 gene variants with Alzheimer's disease.
SORL1 gene variants were described as risk factor of Alzheimer's disease (AD) additionally SORL1 gene variants were associated with altered Abeta(42) 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.
Kölsch
Heike
H
Department of Psychiatry, University of Bonn, Bonn, Germany. heike.koelsch@ukb.uni-bonn.de
Jessen
Frank
F
Wiltfang
Jens
J
Lewczuk
Piotr
P
Dichgans
Martin
M
Teipel
Stefan J
SJ
Kornhuber
Johannes
J
Frölich
Lutz
L
Heuser
Isabella
I
Peters
Oliver
O
Wiese
Birgitt
B
Kaduszkiewicz
Hanna
H
van den Bussche
Hendrik
H
Hüll
Michael
M
Kurz
Alexander
A
Rüther
Eckhart
E
Henn
Fritz A
FA
Maier
Wolfgang
W
D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012044:Regression Analysis
D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human