Home LiteratureArticle Details

PMID: 10051007 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Age of onset in Huntington disease: sex specific influence of apolipoprotein E genotype and normal CAG repeat length.

Journal of medical genetics ·Vol. 36 ·No. 2 ·1999-02-00 ·Pages 108-11

Kehoe P, Krawczak M, Harper PS, Owen MJ, Jones AL

Abstract

Age of onset (AO) of Huntington disease (HD) is known to be correlated with the length of an expanded CAG repeat in the HD gene. Apolipoprotein E (APOE) genotype, in turn, is known to influence AO in Alzheimer disease, rendering the APOE gene a likely candidate to affect AO in other neurological diseases too. We therefore determined APOE genotype and normal CAG repeat length in the HD gene for 138 HD patients who were previously analysed with respect to CAG repeat length. Genotyping for APOE was performed blind to clinical information. In addition to highlighting the effect of the normal repeat length upon AO in maternally inherited HD and in male patients, we show that the APOE epsilon2epsilon3 genotype is associated with significantly earlier AO in males than in females. Such a sex difference in AO was not apparent for any of the other APOE genotypes. Our findings suggest that subtle differences in the course of the neurodegeneration in HD may allow interacting genes to exert gender specific effects upon AO.

MeSH Terms

Age of Onset Anticipation, Genetic Apolipoproteins E/genetics Female Genetic Variation Genotype Humans Huntington Disease/genetics Male Models, Statistical Sex Factors Survival Trinucleotide Repeats

Chemicals

Apolipoproteins E

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Kehoe P

Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK.

Krawczak M

Harper P S

Owen M J

Jones A L

References (23)

23 references, click to expand

Apolipoprotein E genotyping by one-stage PCR.
Lancet. 1991 May 11;337(8750):1158-9 PMID: 1674030
Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain.
Science. 1997 Sep 26;277(5334):1990-3 PMID: 9302293
Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-81 PMID: 8446617
The normal Huntington disease (HD) allele, or a closely linked gene, influences age at onset of HD.
Am J Hum Genet. 1993 Jul;53(1):125-30 PMID: 8317477
Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.
Science. 1993 Aug 13;261(5123):921-3 PMID: 8346443
Trinucleotide repeat length instability and age of onset in Huntington's disease.
Nat Genet. 1993 Aug;4(4):387-92 PMID: 8401587
Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease.
Nat Genet. 1993 Aug;4(4):393-7 PMID: 8401588
The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease.
Nat Genet. 1993 Aug;4(4):398-403 PMID: 8401589
Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments.
Nature. 1994 Nov 3;372(6501):92-4 PMID: 7969426
Apolipoprotein E is a kinetic but not a thermodynamic inhibitor of amyloid formation: implications for the pathogenesis and treatment of Alzheimer disease.
Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):763-7 PMID: 7846048
Apolipoprotein E genotype in diverse neurodegenerative disorders.
Ann Neurol. 1995 Jul;38(1):131-5 PMID: 7611717
Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta-protein following head injury.
Nat Med. 1995 Feb;1(2):135-7 PMID: 7585009
A huntingtin-associated protein enriched in brain with implications for pathology.
Nature. 1995 Nov 23;378(6555):398-402 PMID: 7477378
Association of apolipoprotein E epsilon 4 allele with bulbar-onset motor neuron disease.
Lancet. 1996 Jan 20;347(8995):159-60 PMID: 8544551
Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH.
Nat Med. 1996 Mar;2(3):347-50 PMID: 8612237
Gender difference in apolipoprotein E-associated risk for familial Alzheimer disease: a possible clue to the higher incidence of Alzheimer disease in women.
Am J Hum Genet. 1996 Apr;58(4):803-11 PMID: 8644745
Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats.
Am J Hum Genet. 1996 Jul;59(1):16-22 PMID: 8659522
Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides.
Nat Genet. 1996 Sep;14(1):55-61 PMID: 8782820
Huntington disease: new insights into the relationship between CAG expansion and disease.
Hum Mol Genet. 1996;5 Spec No:1431-5 PMID: 8875248
Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice.
Cell. 1996 Nov 1;87(3):493-506 PMID: 8898202
Late-onset Huntington's disease: a clinical and molecular study.
Age Ageing. 1994 Nov;23(6):445-8 PMID: 9231935
Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation.
Cell. 1997 Aug 8;90(3):537-48 PMID: 9267033
Covariate-dependent age-at-onset distributions for Huntington disease.
Am J Hum Genet. 1991 Oct;49(4):735-45 PMID: 1832816

Article Info

Journal

Journal of medical genetics

Abbr.

J Med Genet

ISSN

0022-2593

Published

1999-02-00

Pages

108-11

Language

English

Region

England

NLM ID

2985087R

PMCID

PMC1734310

Subset

External Links

PubMed source PMC Full Text View journal details

Analysis Services

Age of onset in Huntington disease: sex specific influence of apolipoprotein E genotype and normal CAG repeat length.

Contact

WeChat Official Account