Abstract
To evaluate the association of ATP-binding cassette subfamily B member 1 (ABCB1) genetic variants with the susceptibility to Alzheimer’s disease (AD), we genotyped the rs1128503 (C1236T), rs2032582 (G2677T/A), and rs1045642 (C3435T) polymorphisms in a case–control sample (234 AD patients, 225 controls). Single-marker analyses revealed a significant association solely for the rs1045642 polymorphism (C/C genotype carriers had increased risk for AD), which remains significant after correction for multiple testing. Haplotype analyses indicated three nominally significant associations which were lost after applying multiple test correction.
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References
Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265
Cascorbi I, Flüh C, Remmler C et al (2013) Association of ATP-binding cassette transporter variants with the risk of Alzheimer’s disease. Pharmacogenomics 14:485–494
Cascorbi I, Gerloff T, Johne A et al (2004) Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther 69:169–174
Chen KD, Chang PT, Ping YH, Lee HC, Yeh CW, Wang PN (2011) Gene expression profiling of peripheral blood leukocytes identifies and validates ABCB1 as a novel biomarker for Alzheimer’s disease. Neurobiol Dis 43:698–705
Cirrito JR, Deane R, Fagan AM et al (2005) P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer’s disease mouse model. J Clin Invest 115:3285–3290
Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Erlbaum Associates Inc., Hillsdale, New Jersey, pp 216–226
Faul F, Erdfelder E, Lang AG, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191
Frankfort SV, Doodeman VD, Bakker R et al (2006) ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients. Mol Neurodegener 1:13
Frankfort SV, van Campen JP, Tulner LR, Beijnen JH (2008) Serum amyloid beta peptides in patients with dementia and age-matched non-demented controls as detected by surface-enhanced laser desorption ionisation-time of flight mass spectrometry (SELDI-TOF MS). Curr Clin Pharmacol 3:144–154
Hoffmeyer S, Burk O, von Richter O et al (2000) Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A 97:3473–3478
Jeynes B, Provias J (2011) An investigation into the role of P-glycoprotein in Alzheimer’s disease lesion pathogenesis. Neurosci Lett 487:389–393
Kohen R, Shofer JB, Korvatska O et al (2011) ABCB1 genotype and CSF beta-amyloid in Alzheimer disease. J Geriatr Psychiatry Neurol 24:63–66
Kuhnke D, Jedlitschky G, Grube M et al (2007) MDR1-P-glycoprotein (ABCB1) mediates transport of Alzheimer’s amyloid-beta peptides—implications for the mechanisms of beta-amyloid clearance at the blood-brain barrier. Brain Pathol 17:347–353
Lam FC, Liu R, Lu P et al (2001) Beta-amyloid efflux mediated by p-glycoprotein. J Neurochem 76:1121–1128
Li H, Wetten S, Li L et al (2008) Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. Arch Neurol 65:45–53
Mawuenyega KG, Sigurdson W, Ovod V et al (2010) Decreased clearance of CNS beta-amyloid in Alzheimer’s disease. Science 330:1774
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944
Nakamura T, Sakaeda T, Horinouchi M et al (2002) Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects. Clin Pharmacol Ther 71:297–303
Pahnke J, Wolkenhauer O, Krohn MA, Walker LC (2008) Clinico-pathologic function of cerebral ABC transporters—implications for the pathogenesis of Alzheimer’s disease. Curr Alzheimer Res 5:396–405
Reiman EM, Webster JA, Myers AJ et al (2007) GAB2 alleles modify Alzheimer’s risk in APOE epsilon4 carriers. Neuron 54:713–720
Sakaeda T, Nakamura T, Horinouchi M et al (2001) MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects. Pharm Res 18:1400–1404
Sipeky C, Csongei V, Jaromi L et al (2011) Genetic variability and haplotype profile of MDR1 (ABCB1) in Roma and Hungarian population samples with a review of the literature. Drug Metab Pharmacokinet 26:206–215
Van Assema DME, Lubberink M, Rizzu P et al. (2012) Blood–brain barrier P-glycoprotein function in healthy subjects and Alzheimer’s disease patients: effect of polymorphisms in the ABCB1 gene
Vogelgesang S, Cascorbi I, Schroeder E et al (2002) Deposition of Alzheimer’s beta-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humans. Pharmacogenetics 12:535–541
Wang D, Johnson AD, Papp AC, Kroetz DL, Sadee W (2005) Multidrug resistance polypeptide 1 (MDR1, ABCB1) variant 3435C > T affects mRNA stability. Pharmacogenet Genomics 15:693–704
Wolf A, Bauer B, Hartz AM (2012) ABC transporters and the Alzheimer’s disease enigma. Front Psychiatry 3:54
Acknowledgments
The authors are grateful to the participants of this study for their cooperation. This work was supported by a grant from TÁMOP-4.2.2A-11/1/KONV-2012-0052.
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Fehér, Á., Juhász, A., Pákáski, M. et al. ABCB1 C3435T Polymorphism Influences the Risk for Alzheimer’s Disease. J Mol Neurosci 54, 826–829 (2014). https://doi.org/10.1007/s12031-014-0427-z
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DOI: https://doi.org/10.1007/s12031-014-0427-z