LRP-associated protein gene (LRPAP1) and susceptibility to degenerative dementia

Genes Brain Behav. 2008 Nov;7(8):943-50. doi: 10.1111/j.1601-183X.2008.00436.x. Epub 2008 Aug 21.

Abstract

Difference in genetic makeup of lipid metabolizing proteins may increase susceptibility to dementia. The aim of this study was to investigate variations in two lipid metabolizing genes, low-density lipoprotein receptor-related protein-associated protein gene (LRPAP) and apolipoprotein E (APOE), in vascular and degenerative dementias. This hospital-based association study included 147 patients with dementia and 163 age-matched controls. Genotyping for LRPAP1 intron 5 insertion/deletion and APOEHhaI polymorphism was carried out by polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism method. The frequency of DD genotype and *D allele of LRPAP gene was high in degenerative dementias compared with controls (76.6% vs. 44.8% and 86.4% vs. 69.3%, respectively) suggesting increased susceptibility [P < 0.0001, odds ratio (OR) =3.76 for DD genotype and P < 0.0001, OR = 2.80 for D allele]. Vascular dementia patients showed statistically insignificant but increasing trend for allele I (40.0% vs. 30.7%). We also observed significant association of APOEepsilon4 allele with degenerative dementias (P < 0.0001, OR =5.35). Our study suggests that LRPAP1-D and APOE E4 alleles significantly increase the susceptibility to degenerative dementias.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Apolipoprotein E4 / genetics
  • Apolipoprotein E4 / metabolism
  • Brain Chemistry / genetics*
  • DNA Mutational Analysis
  • Dementia / genetics*
  • Dementia / metabolism
  • Dementia / physiopathology
  • Dementia, Vascular / genetics
  • Dementia, Vascular / metabolism
  • Dementia, Vascular / physiopathology
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Humans
  • LDL-Receptor Related Protein-Associated Protein / genetics*
  • LDL-Receptor Related Protein-Associated Protein / metabolism
  • Lipid Metabolism Disorders / genetics*
  • Lipid Metabolism Disorders / metabolism
  • Lipid Metabolism Disorders / physiopathology
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Polymorphism, Genetic / genetics
  • Polymorphism, Restriction Fragment Length

Substances

  • Apolipoprotein E4
  • LDL-Receptor Related Protein-Associated Protein