ABCA1 Transporter: Disease Association:
Alzheimer’s Disease (AD):
- Overexpression of hydroxy-methylglutaryl-coenzyme A reductase (HMGCR) and underexpression of ABCA1 may cause increased cholesterol accumulation, Abeta production, and higher AD risk. Those with both the HMGCR (5′-UTR) GG genotype and the ABCA1 (-14) TT genotype, or the ABCA1 (-477) TT genotype may have a higher risk of having AD than those without these risk genotypes.
(Interaction between HMGCR and ABCA1 cholesterol-related genes modulates Alzheimer’s disease risk. Rodríguez-Rodríguez E, Mateo I, Infante J, Llorca J, García-Gorostiaga I, Vázquez-Higuera JL, Sánchez-Juan P, Berciano J, Combarros O. Brain Res. 2009 Jul 14;1280:166-71. Epub 2009 May 14.PMID: 19446537)
- The SNP rs2297404 may have a significant association with risk of AD, because its position is in the vicinity of a splicing branch site.
(A novel intronic polymorphism of ABCA1 gene reveals risk for sporadic Alzheimer’s disease in Chinese. Chu LW, Li Y, Li Z, Tang AY, Cheung BM, Leung RY, Yik PY, Jin DY, Song YQ. Am J Med Genet B Neuropsychiatr Genet. 2007 Dec 5;144B(8):1007-13.PMID: 17510949)
- The development of AD might be connected with a qualitative change of the ABCA1 protein due to coding region variants (219K, 883I, and 1587R). It may also be caused by a quantitative change in ABCA1 expression due to promoter region variant (-14T) together with the APOE epsilon4 allele.
(Association of genetic variants of ABCA1 with Alzheimer’s disease risk. Rodríguez-Rodríguez E, Mateo I, Llorca J, Sánchez-Quintana C, Infante J, García-Gorostiaga I, Sánchez-Juan P, Berciano J, Combarros O. Am J Med Genet B Neuropsychiatr Genet. 2007 Oct 5;144B(7):964-8.PMID: 17510946)
- Transcription factors nuclear liver X receptors (LXR), together with ABCA1 and other genes may affect AD pathogenesis through regulatory effects on intracellular cholesterol content and cholesterol efflux. Anti-inflammatory mechanisms may also be involved.
(Role of LXR and ABCA1 in the pathogenesis of Alzheimer’s disease – implications for a new therapeutic approach. Koldamova R, Lefterov I. Curr Alzheimer Res. 2007 Apr;4(2):171-8. Review.PMID: 17430243)
- KK genotype or K allele (G–>A (R219K), RK+KK genotypes) of ABCA1 gene be protective with decreased AD risks in Chinese.
(Polymorphisms of cholesterol metabolism genes CYP46 and ABCA1 and the risk of sporadic Alzheimer’s disease in Chinese. Wang F, Jia J. Brain Res. 2007 May 25;1147:34-8. Epub 2007 Feb 8.PMID: 17335784)
- There may be a weak association between the SNP rs2230806 with AD in a sibpair series.
(ABCA1 polymorphisms and Alzheimer’s disease. Wavrant-De Vrièze F, Compton D, Womick M, Arepalli S, Adighibe O, Li L, Pérez-Tur J, Hardy J. Neurosci Lett. 2007 Apr 12;416(2):180-3. Epub 2007 Feb 7.PMID: 17324514)
- There may be a gender-specific, and APOE and UBQLN1 independent relationship between the ABCA1/R219K polymorphism and late-onset AD (LOAD) in American white populations.
(Gender-specific association of ATP-binding cassette transporter 1 (ABCA1) polymorphisms with the risk of late-onset Alzheimer’s disease. Sundar PD, Feingold E, Minster RL, DeKosky ST, Kamboh MI. Neurobiol Aging. 2007 Jun;28(6):856-62. Epub 2006 May 24.PMID: 16725228)
- The genetic variability of ABCA1 (e.g., R219K, SNP rs2234884) may influence the development of AD through interfering with CNS cholesterol homeostasis.
(ABCA1 modulates CSF cholesterol levels and influences the age at onset of Alzheimer’s disease. Wollmer MA, Streffer JR, Lütjohann D, Tsolaki M, Iakovidou V, Hegi T, Pasch T, Jung HH, Bergmann K, Nitsch RM, Hock C, Papassotiropoulos A. Neurobiol Aging. 2003 May-Jun;24(3):421-6.PMID: 12600718)
