title: Genetic association between polymorphisms of Pen2 gene and late onset Alzheimer's disease in the North Chinese population.
abstract: Presenilin enhancer 2 (Pen2) is a subunit of the gamma-secretase complex which cleaves amyloid precursor protein (APP) to generate amyloid beta (Abeta). We performed a systematic screening of all Pen2 exons and introns using direct sequencing to assess its role in the risk of developing late onset Alzheimer's disease (LOAD). 947 subjects (LOAD: 467;
  
  
  METHODS
  480) were recruited for this study. We obtained three polymorphisms: rs10402601, rs3817622, and rs2293688. Among these three polymorphisms, there was an interaction between rs3817622 and apolipoprotein E (APOE) genotypes (P=0.002). In the subjects with APOE 4 allele, there was a significant difference in the distribution of alleles (P=0.003) and genotypes (P=0.007) between LOAD and control groups. ORs [95% confidence interval (CI)] of allele A and T/A+A/A genotypes were respectively 4.720 (1.517-10.654) and 3.886 (1.381-10.932) with allele T and genotype T/T as a reference. Our results suggest that there is an association between rs3817622 and the development of LOAD in APOE epsilon4 carriers within the northern Chinese population. It is possible allele A of the Pen2 gene increases the risk for LOAD.
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Beijing, PR China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Jia
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.forename: Haiyan
authors.initials: H
authors.lastname: L V
authors.forename: Weishan
authors.initials: W
authors.lastname: Wang
authors.forename: Chunkui
authors.initials: C
authors.lastname: Zhou
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Xu
authors.forename: Lingling
authors.initials: L
authors.lastname: Wang
authors.forename: Jianping
authors.initials: J
authors.lastname: Jia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D002681:China / Q000453:epidemiology; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D044382:Population Groups
chemical_list: D053327:Apolipoprotein E4; D008565:Membrane Proteins; C469349:PSENEN protein, human; D053829:Amyloid Precursor Protein Secretases