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.
Department of Psychiatry, University of Bonn, Bonn, Germany. heike.koelsch@ukb.uni-bonn.de
Heike
H
Kölsch
Frank
F
Jessen
Jens
J
Wiltfang
Piotr
P
Lewczuk
Martin
M
Dichgans
Stefan J
SJ
Teipel
Johannes
J
Kornhuber
Lutz
L
Frölich
Isabella
I
Heuser
Oliver
O
Peters
Birgitt
B
Wiese
Hanna
H
Kaduszkiewicz
Hendrik
H
van den Bussche
Michael
M
Hüll
Alexander
A
Kurz
Eckhart
E
Rüther
Fritz A
FA
Henn
Wolfgang
W
Maier
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