ABCA1 rs2230805 and rs2230806 common gene variants are associated with Alzheimer's disease

Ágnes Fehér, Zsófia Giricz, Anna Juhász, M. Pákáski, Z. Janka, János Kálmán

Research output: Contribution to journalArticle

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Abstract

The ATP-binding cassette, sub-family A, member 1 gene (ABCA1) is a relevant positional and functional candidate gene for Alzheimer's disease (AD). A case-control association study of genetic variations covering the ABCA1 locus was performed in relation to AD risk in a Hungarian sample. Five single nucleotide polymorphisms (rs2422493: C-477T, rs2740483: G-17C, rs2230805: G474A/L158L, rs2230806: G656A/R219 K and rs2066718: G2311A/V771 M) were genotyped in 431 AD patients and 302 cognitively healthy, elderly controls. In single marker analysis, significant associations were found in the case of rs2230805 and rs2230806 polymorphisms: the minor A allele containing genotypes for both polymorphisms were more frequent in the control compared to the AD group. Haplotype analysis revealed that rs2230805, rs2230806 and rs2066718 polymorphisms created a linkage disequilibrium (LD) block with a strong LD between rs2230805 and rs2230806 polymorphisms. In the haplotype risk association tests, A-A-G haplotype of the rs2230805-rs2230806-rs2066718 polymorphisms was found to be nominally significantly more frequent in the control group. After correcting p values for multiple testing, only the effects of the rs2230805 and rs2230806 polymorphisms remained significant in the recessive model suggesting a modest protective effect of their minor alleles in AD, which should be interpreted with considerable caution, until further studies elucidate their role in AD pathology.

Original languageEnglish
Pages (from-to)79-83
Number of pages5
JournalNeuroscience Letters
Volume664
DOIs
Publication statusPublished - Jan 18 2018

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Alzheimer Disease
Haplotypes
Genes
Linkage Disequilibrium
Brilliant Lake Red R
ATP Binding Cassette Transporter 1
Alleles
Single Nucleotide Polymorphism
Case-Control Studies
Genotype
Pathology
Control Groups

Keywords

  • Alzheimer's disease
  • Association study
  • ATP-binding cassette transporter subfamily A member 1 (ABCA1)
  • Single nucleotide polymorphism (SNP)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

ABCA1 rs2230805 and rs2230806 common gene variants are associated with Alzheimer's disease. / Fehér, Ágnes; Giricz, Zsófia; Juhász, Anna; Pákáski, M.; Janka, Z.; Kálmán, János.

In: Neuroscience Letters, Vol. 664, 18.01.2018, p. 79-83.

Research output: Contribution to journalArticle

Fehér, Ágnes ; Giricz, Zsófia ; Juhász, Anna ; Pákáski, M. ; Janka, Z. ; Kálmán, János. / ABCA1 rs2230805 and rs2230806 common gene variants are associated with Alzheimer's disease. In: Neuroscience Letters. 2018 ; Vol. 664. pp. 79-83.
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abstract = "The ATP-binding cassette, sub-family A, member 1 gene (ABCA1) is a relevant positional and functional candidate gene for Alzheimer's disease (AD). A case-control association study of genetic variations covering the ABCA1 locus was performed in relation to AD risk in a Hungarian sample. Five single nucleotide polymorphisms (rs2422493: C-477T, rs2740483: G-17C, rs2230805: G474A/L158L, rs2230806: G656A/R219 K and rs2066718: G2311A/V771 M) were genotyped in 431 AD patients and 302 cognitively healthy, elderly controls. In single marker analysis, significant associations were found in the case of rs2230805 and rs2230806 polymorphisms: the minor A allele containing genotypes for both polymorphisms were more frequent in the control compared to the AD group. Haplotype analysis revealed that rs2230805, rs2230806 and rs2066718 polymorphisms created a linkage disequilibrium (LD) block with a strong LD between rs2230805 and rs2230806 polymorphisms. In the haplotype risk association tests, A-A-G haplotype of the rs2230805-rs2230806-rs2066718 polymorphisms was found to be nominally significantly more frequent in the control group. After correcting p values for multiple testing, only the effects of the rs2230805 and rs2230806 polymorphisms remained significant in the recessive model suggesting a modest protective effect of their minor alleles in AD, which should be interpreted with considerable caution, until further studies elucidate their role in AD pathology.",
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