α2-macroglobulin exon 24 (Val-1000-Ile) polymorphism is not associated with late-onset sporadic Alzheimer's dementia in the Hungarian population

Z. Janka, A. Juhász, A. Rimanóczy, K. Boda, János Márki-Zay, Miklós Palotás, Ilona Kuk, Magdolna Zöllei, Katalin Jakab, J. Kálmán

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Several lines of biochemical evidence support a role of α2-macroglobulin (A2M) in the pathogenesis of Alzheimer's dementia (AD). A2M participates in the general defence mechanism against proteinases and it is supposed to be involved in the degradation of beta-amyloid peptide (βAP). Furthermore, A2M has been shown to reduce βAP fibril formation, and it is upregulated in the acute-phase inflammatory response like the process occurring in the AD brain. The exon 18 splice acceptor deletion polymorphism and the exon 24 (Val-1000-Ile) GG genotype were reported to be associated with AD, but the results are contradictory. Since the Hungarian population is genetically distinct from the other European ethnic groups, we examined whether the risk for developing AD is increased in the A2M GG carriers. The interaction of apolipoprotein E (apoE) and A2M polymorphisms was also examined. The distribution of A2M genotypes and alleles in the entire data set was consistent with the previous negative observations in which A and G allelic frequencies were comparable in both groups (72% and 28% in the AD population, and 72% and 28% in the control population, respectively). The GG genotype was over-represented (14%) only in the apoE ε4 non-carrier subgroup of AD probands (7% in the control group), but the difference was not significant. Our data suggest that, although A2M has an important role in the AD-specific neurodegenerative process, its exon 24 Val-1000-Ile polymorphism is not likely to be associated with late-onset sporadic AD in the Hungarian population.

Original languageEnglish
Pages (from-to)49-54
Number of pages6
JournalPsychiatric Genetics
Volume12
Issue number1
DOIs
Publication statusPublished - 2002

Fingerprint

Macroglobulins
Exons
Alzheimer Disease
Population
Genotype
Apolipoprotein E4
Acute-Phase Reaction
Amyloid beta-Peptides
Apolipoproteins E
Ethnic Groups
Amyloid
Peptide Hydrolases
Alleles
Control Groups
Peptides
Brain

Keywords

  • α2 macroglobulin
  • Alzheimer's dementia
  • Apolipoprotein E
  • Exon 24
  • Polymorphism
  • Risk factor

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Genetics
  • Neuroscience(all)

Cite this

α2-macroglobulin exon 24 (Val-1000-Ile) polymorphism is not associated with late-onset sporadic Alzheimer's dementia in the Hungarian population. / Janka, Z.; Juhász, A.; Rimanóczy, A.; Boda, K.; Márki-Zay, János; Palotás, Miklós; Kuk, Ilona; Zöllei, Magdolna; Jakab, Katalin; Kálmán, J.

In: Psychiatric Genetics, Vol. 12, No. 1, 2002, p. 49-54.

Research output: Contribution to journalArticle

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abstract = "Several lines of biochemical evidence support a role of α2-macroglobulin (A2M) in the pathogenesis of Alzheimer's dementia (AD). A2M participates in the general defence mechanism against proteinases and it is supposed to be involved in the degradation of beta-amyloid peptide (βAP). Furthermore, A2M has been shown to reduce βAP fibril formation, and it is upregulated in the acute-phase inflammatory response like the process occurring in the AD brain. The exon 18 splice acceptor deletion polymorphism and the exon 24 (Val-1000-Ile) GG genotype were reported to be associated with AD, but the results are contradictory. Since the Hungarian population is genetically distinct from the other European ethnic groups, we examined whether the risk for developing AD is increased in the A2M GG carriers. The interaction of apolipoprotein E (apoE) and A2M polymorphisms was also examined. The distribution of A2M genotypes and alleles in the entire data set was consistent with the previous negative observations in which A and G allelic frequencies were comparable in both groups (72{\%} and 28{\%} in the AD population, and 72{\%} and 28{\%} in the control population, respectively). The GG genotype was over-represented (14{\%}) only in the apoE ε4 non-carrier subgroup of AD probands (7{\%} in the control group), but the difference was not significant. Our data suggest that, although A2M has an important role in the AD-specific neurodegenerative process, its exon 24 Val-1000-Ile polymorphism is not likely to be associated with late-onset sporadic AD in the Hungarian population.",
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T1 - α2-macroglobulin exon 24 (Val-1000-Ile) polymorphism is not associated with late-onset sporadic Alzheimer's dementia in the Hungarian population

AU - Janka, Z.

AU - Juhász, A.

AU - Rimanóczy, A.

AU - Boda, K.

AU - Márki-Zay, János

AU - Palotás, Miklós

AU - Kuk, Ilona

AU - Zöllei, Magdolna

AU - Jakab, Katalin

AU - Kálmán, J.

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AB - Several lines of biochemical evidence support a role of α2-macroglobulin (A2M) in the pathogenesis of Alzheimer's dementia (AD). A2M participates in the general defence mechanism against proteinases and it is supposed to be involved in the degradation of beta-amyloid peptide (βAP). Furthermore, A2M has been shown to reduce βAP fibril formation, and it is upregulated in the acute-phase inflammatory response like the process occurring in the AD brain. The exon 18 splice acceptor deletion polymorphism and the exon 24 (Val-1000-Ile) GG genotype were reported to be associated with AD, but the results are contradictory. Since the Hungarian population is genetically distinct from the other European ethnic groups, we examined whether the risk for developing AD is increased in the A2M GG carriers. The interaction of apolipoprotein E (apoE) and A2M polymorphisms was also examined. The distribution of A2M genotypes and alleles in the entire data set was consistent with the previous negative observations in which A and G allelic frequencies were comparable in both groups (72% and 28% in the AD population, and 72% and 28% in the control population, respectively). The GG genotype was over-represented (14%) only in the apoE ε4 non-carrier subgroup of AD probands (7% in the control group), but the difference was not significant. Our data suggest that, although A2M has an important role in the AD-specific neurodegenerative process, its exon 24 Val-1000-Ile polymorphism is not likely to be associated with late-onset sporadic AD in the Hungarian population.

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KW - Risk factor

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