title: Association of ATP-binding cassette transporter variants with the risk of Alzheimer's disease.
abstract: OBJECTIVE
  A number of studies have demonstrated that ABCB1 and BCRP (ABCG2) actively transport Aβ. We aimed to investigate the association of genetic variants of selected multidrug transporters with Alzheimer's disease (AD) in histopathologically confirmed AD cases and controls.
  
  
  METHODS
  DNA from brain tissue of 71 AD cases with Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropathological stages B/C and 81 controls was genotyped for selected variants in ABCA1, ABCA7, ABCB1, ABCC2 and ABCG2. In addition, the APOE4 status was analyzed.
  
  
  RESULTS
  The novel ABCA7 SNP, rs3752246, tended to be associated with AD in our study. Variants in ABCB1 were significantly less frequent in AD cases older than 65 years of age and among females. This association of ABCB1 2677G>T (rs2032582) was more pronounced in APOE4-negative cases (p = 0.005). However, only ABCC2 3972C>T (rs3740066) was significantly associated with AD risk after logistic regression analysis including all variants. Other transporters showed a lack of association.
  
  
  CONCLUSIONS
  Our results support the hypothesis that ABCB1 and possibly other ABC-transporters are involved in the process of Aβ accumulation in the aging brain and may modulate the risk for AD in an allele-specific manner, and thus might represent a new target for prevention and treatment of AD.
authors.affiliation: Institute of Experimental & Clinical Pharmacology, University Hospital Schleswig-Holstein, Arnold-Heller-Str. 3, Bldg 30, D-24105 Kiel, Germany. cascorbi@pharmakologie.uni-kiel.de
authors.forename: Ingolf
authors.initials: I
authors.lastname: Cascorbi
authors.forename: Charlotte
authors.initials: C
authors.lastname: Flüh
authors.forename: Cornelia
authors.initials: C
authors.lastname: Remmler
authors.forename: Sierk
authors.initials: S
authors.lastname: Haenisch
authors.forename: Frank
authors.initials: F
authors.lastname: Faltraco
authors.forename: Maria
authors.initials: M
authors.lastname: Grumbt
authors.forename: Michele
authors.initials: M
authors.lastname: Peters
authors.forename: Anja
authors.initials: A
authors.lastname: Brenn
authors.forename: Dietmar Rudolf
authors.initials: DR
authors.lastname: Thal
authors.forename: Rolf Wolfgang
authors.initials: RW
authors.lastname: Warzok
authors.forename: Silke
authors.initials: S
authors.lastname: Vogelgesang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C411895:ABCA7 protein, human; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human