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The Alzheimer's associated 5' region of the SORL1 gene cis regulates SORL1 transcripts expression.

Publication ,  Journal Article
McCarthy, JJ; Saith, S; Linnertz, C; Burke, JR; Hulette, CM; Welsh-Bohmer, KA; Chiba-Falek, O
Published in: Neurobiol Aging
July 2012

SORL1 has been identified as a major contributor to late onset Alzheimer's disease (LOAD). We test whether genetic variability in the 5' of SORL1 gene modulates the risk to develop LOAD via regulation of SORL1-messenger ribonucleic acid (mRNA) expression and splicing. Two brain structures, differentially vulnerable to LOAD pathology, were examined in 144 brain samples from 92 neurologically normal individuals. The temporal cortex, which is more susceptible to Alzheimer's pathology, demonstrated ∼2-fold increase in SORL1-mRNA levels in carriers of the minor alleles at single nucleotide polymorphisms (SNPs), rs7945931 and rs2298525, compared with noncarriers. No genetic effect on total-SORL1-mRNA levels was detected in the frontal cortex. However, rs11600875 minor allele was associated with significantly increased levels of exon-2 skipping, but only in frontal cortex. No correlation of SORL1-mRNAs expression was found between frontal and temporal cortexes. Collectively, these indicate the brain region specificity of the genetic regulation of SORL1 expression. Our results suggest that genetic regulation of SORL1 expression plays a role in disease risk and may be responsible for the reported LOAD associations. Further studies to detect the actual pathogenic variant/s are necessary.

Duke Scholars

Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

July 2012

Volume

33

Issue

7

Start / End Page

1485.e1 / 1485.e8

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Temporal Lobe
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Middle Aged
  • Membrane Transport Proteins
  • Male
  • LDL-Receptor Related Proteins
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
McCarthy, J. J., Saith, S., Linnertz, C., Burke, J. R., Hulette, C. M., Welsh-Bohmer, K. A., & Chiba-Falek, O. (2012). The Alzheimer's associated 5' region of the SORL1 gene cis regulates SORL1 transcripts expression. Neurobiol Aging, 33(7), 1485.e1-1485.e8. https://doi.org/10.1016/j.neurobiolaging.2010.10.004
McCarthy, Jeanette J., Sunita Saith, Colton Linnertz, James R. Burke, Christine M. Hulette, Kathleen A. Welsh-Bohmer, and Ornit Chiba-Falek. “The Alzheimer's associated 5' region of the SORL1 gene cis regulates SORL1 transcripts expression.Neurobiol Aging 33, no. 7 (July 2012): 1485.e1-1485.e8. https://doi.org/10.1016/j.neurobiolaging.2010.10.004.
McCarthy JJ, Saith S, Linnertz C, Burke JR, Hulette CM, Welsh-Bohmer KA, et al. The Alzheimer's associated 5' region of the SORL1 gene cis regulates SORL1 transcripts expression. Neurobiol Aging. 2012 Jul;33(7):1485.e1-1485.e8.
McCarthy, Jeanette J., et al. “The Alzheimer's associated 5' region of the SORL1 gene cis regulates SORL1 transcripts expression.Neurobiol Aging, vol. 33, no. 7, July 2012, pp. 1485.e1-1485.e8. Pubmed, doi:10.1016/j.neurobiolaging.2010.10.004.
McCarthy JJ, Saith S, Linnertz C, Burke JR, Hulette CM, Welsh-Bohmer KA, Chiba-Falek O. The Alzheimer's associated 5' region of the SORL1 gene cis regulates SORL1 transcripts expression. Neurobiol Aging. 2012 Jul;33(7):1485.e1-1485.e8.
Journal cover image

Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

July 2012

Volume

33

Issue

7

Start / End Page

1485.e1 / 1485.e8

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Temporal Lobe
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Middle Aged
  • Membrane Transport Proteins
  • Male
  • LDL-Receptor Related Proteins
  • Humans