Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer's disease

Danny Cheng, R. Huang, I. S. Lanham, H. M. Calhcart, M. Howard, E. H. Corder, S. E. Poduslo

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: Multiple genes have been provisionally associated with Alzheimer's disease, including the coding polymorphisms in exons 8 and 13 in the low density lipoprotein receptor gene (LDLR), situated on chromosome 19p13.2. Methods: The sample groups consisted of 180 AD patients and 141 control spouses. We carried out genotyping of LDLR8 and LDLR13. Results: The LDLR8 GG genotype was common, found in 84% of the unaffected control subjects and 91% of the AD patients in our study. There was a ninefold elevation in risk associated with GG:CC versus A- and T- among APOE4+ subjects when compared with APOE4- subjects (odds ratio 9.3; 95% confidence interval 1.8 to 48.2). With the additional information on LDLR polymorphism, we defined an overall 12 fold elevation in risk for APOE4 in combination with LDLR GG:CC (11.9; 2.8 to 50.0; Fisher's exact test, p = 0.0002; standard power 0.999), compared with other subjects lacking all three of these polymorphisms. Conclusion: These results imply a functional interaction between ApoE and LDL receptor proteins that determines risk for Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)129-131
Number of pages3
JournalJournal of Medical Genetics
Volume42
Issue number2
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Cheng, D., Huang, R., Lanham, I. S., Calhcart, H. M., Howard, M., Corder, E. H., & Poduslo, S. E. (2005). Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer's disease. Journal of Medical Genetics, 42(2), 129-131. https://doi.org/10.1136/jmg.2004.024968