Association of ATP-binding cassette transporter variants with the risk of Alzheimer's disease. (April 2013)

• Record Type: Journal Article
• Authors: Cascorbi, Ingolf; Flüh, Charlotte; Remmler, Cornelia; Haenisch, Sierk; Faltraco, Frank; Grumbt, Maria; Peters, Michele; Brenn, Anja; Thal, Dietmar Rudolf; Warzok, Rolf Wolfgang; Vogelgesang, Silke
• Is Part Of: Pharmacogenomics. Volume 14:Number 5(2013)
• Page Start: 485
• Page End: 494
• Publication Date: 2013-04
• Subjects: β-amyloid -- ABCA1 -- ABCA7 -- ABCC2 -- Alzheimer's -- APOE -- BRCP -- P-glycoprotein; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.13.18
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: 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.Materials & 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.Conclusion: 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. Original submitted 8 October 2012; Revision submitted 22 January 2013