No association between the HLA-A2 allele and Alzheimer disease

Gary W. Small, William K Scott, Scott Komo, Larry H. Yamaoka, Lindsay A. Farrer, Sanford H. Auerbach, Ann M. Saunders, Allen D. Roses, Jonathan L. Haines, Margaret A Pericak-Vance

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The apolipoprotein E (APOE)-4 allele is a major risk factor for late- onset Alzheimer disease (AD), but it does not account for all the genetic variation in late-onset AD; thus, other genetic markers must be examined. Previous studies suggest an HLA-A2 allele association with risk and earlier onset age of AD. Because these effects may be additive to those of APOE-4, we studied HLA-A2 and APOE-4 frequencies in AD patients and cognitively intact controls. A total of 712 unrelated Caucasian subjects included 479 patients with AD (435 sporadic, 44 familial) and 233 controls. Patients (mean ± SD age 73.9 ± 7.9 years, range 42-93 years) had probable AD, according to standard diagnostic criteria; controls (mean ± SD age 70.4 ± 8.5 years, range 37-92 years) were cognitively intact. APOE and HLA-A2 typing used polymerase chain reaction to indicate the number of APOE-4 alleles present as well as the presence (A1/A2, A2/A2 genotypes) or absence (A1/A1 genotype) of HLA-A2. A two-way analysis of variance was used to assess the effect of the HLA-A2 allele on age at onset of dementia. No association between HLA-A2 and APOE-4 was found, and the presence of HLA-A2 allele did not increase AD risk. There was also no evidence for an association between HLA-A2 and earlier onset age of AD. Examination age, sex, family history of AD, and recruitment site had no influence on these results. In conclusion, the HLA-A2 allele did not influence AD risk or onset age in this study population. A2 heterozygosity, and population differences, including stratification sub- structures, and other undetermined factors could contribute to discrepant findings among studies.

Original languageEnglish
Pages (from-to)177-182
Number of pages6
JournalNeurogenetics
Volume2
Issue number3
DOIs
StatePublished - Oct 26 1999
Externally publishedYes

Fingerprint

HLA-A2 Antigen
Alzheimer Disease
Alleles
Apolipoprotein E4
varespladib methyl
Age of Onset
Genotype
Histocompatibility Testing
Apolipoproteins E
Genetic Markers
Population
Dementia
Analysis of Variance

Keywords

  • Alzheimer disease
  • Apolipoprotein E
  • HLA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

Cite this

No association between the HLA-A2 allele and Alzheimer disease. / Small, Gary W.; Scott, William K; Komo, Scott; Yamaoka, Larry H.; Farrer, Lindsay A.; Auerbach, Sanford H.; Saunders, Ann M.; Roses, Allen D.; Haines, Jonathan L.; Pericak-Vance, Margaret A.

In: Neurogenetics, Vol. 2, No. 3, 26.10.1999, p. 177-182.

Research output: Contribution to journalArticle

Small, GW, Scott, WK, Komo, S, Yamaoka, LH, Farrer, LA, Auerbach, SH, Saunders, AM, Roses, AD, Haines, JL & Pericak-Vance, MA 1999, 'No association between the HLA-A2 allele and Alzheimer disease', Neurogenetics, vol. 2, no. 3, pp. 177-182. https://doi.org/10.1007/s100480050080
Small GW, Scott WK, Komo S, Yamaoka LH, Farrer LA, Auerbach SH et al. No association between the HLA-A2 allele and Alzheimer disease. Neurogenetics. 1999 Oct 26;2(3):177-182. https://doi.org/10.1007/s100480050080
Small, Gary W. ; Scott, William K ; Komo, Scott ; Yamaoka, Larry H. ; Farrer, Lindsay A. ; Auerbach, Sanford H. ; Saunders, Ann M. ; Roses, Allen D. ; Haines, Jonathan L. ; Pericak-Vance, Margaret A. / No association between the HLA-A2 allele and Alzheimer disease. In: Neurogenetics. 1999 ; Vol. 2, No. 3. pp. 177-182.
@article{3f0c3e2419704ab4a94f3c46ef7ff368,
title = "No association between the HLA-A2 allele and Alzheimer disease",
abstract = "The apolipoprotein E (APOE)-4 allele is a major risk factor for late- onset Alzheimer disease (AD), but it does not account for all the genetic variation in late-onset AD; thus, other genetic markers must be examined. Previous studies suggest an HLA-A2 allele association with risk and earlier onset age of AD. Because these effects may be additive to those of APOE-4, we studied HLA-A2 and APOE-4 frequencies in AD patients and cognitively intact controls. A total of 712 unrelated Caucasian subjects included 479 patients with AD (435 sporadic, 44 familial) and 233 controls. Patients (mean ± SD age 73.9 ± 7.9 years, range 42-93 years) had probable AD, according to standard diagnostic criteria; controls (mean ± SD age 70.4 ± 8.5 years, range 37-92 years) were cognitively intact. APOE and HLA-A2 typing used polymerase chain reaction to indicate the number of APOE-4 alleles present as well as the presence (A1/A2, A2/A2 genotypes) or absence (A1/A1 genotype) of HLA-A2. A two-way analysis of variance was used to assess the effect of the HLA-A2 allele on age at onset of dementia. No association between HLA-A2 and APOE-4 was found, and the presence of HLA-A2 allele did not increase AD risk. There was also no evidence for an association between HLA-A2 and earlier onset age of AD. Examination age, sex, family history of AD, and recruitment site had no influence on these results. In conclusion, the HLA-A2 allele did not influence AD risk or onset age in this study population. A2 heterozygosity, and population differences, including stratification sub- structures, and other undetermined factors could contribute to discrepant findings among studies.",
keywords = "Alzheimer disease, Apolipoprotein E, HLA",
author = "Small, {Gary W.} and Scott, {William K} and Scott Komo and Yamaoka, {Larry H.} and Farrer, {Lindsay A.} and Auerbach, {Sanford H.} and Saunders, {Ann M.} and Roses, {Allen D.} and Haines, {Jonathan L.} and Pericak-Vance, {Margaret A}",
year = "1999",
month = "10",
day = "26",
doi = "10.1007/s100480050080",
language = "English",
volume = "2",
pages = "177--182",
journal = "Neurogenetics",
issn = "1364-6745",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - No association between the HLA-A2 allele and Alzheimer disease

AU - Small, Gary W.

AU - Scott, William K

AU - Komo, Scott

AU - Yamaoka, Larry H.

AU - Farrer, Lindsay A.

AU - Auerbach, Sanford H.

AU - Saunders, Ann M.

AU - Roses, Allen D.

AU - Haines, Jonathan L.

AU - Pericak-Vance, Margaret A

PY - 1999/10/26

Y1 - 1999/10/26

N2 - The apolipoprotein E (APOE)-4 allele is a major risk factor for late- onset Alzheimer disease (AD), but it does not account for all the genetic variation in late-onset AD; thus, other genetic markers must be examined. Previous studies suggest an HLA-A2 allele association with risk and earlier onset age of AD. Because these effects may be additive to those of APOE-4, we studied HLA-A2 and APOE-4 frequencies in AD patients and cognitively intact controls. A total of 712 unrelated Caucasian subjects included 479 patients with AD (435 sporadic, 44 familial) and 233 controls. Patients (mean ± SD age 73.9 ± 7.9 years, range 42-93 years) had probable AD, according to standard diagnostic criteria; controls (mean ± SD age 70.4 ± 8.5 years, range 37-92 years) were cognitively intact. APOE and HLA-A2 typing used polymerase chain reaction to indicate the number of APOE-4 alleles present as well as the presence (A1/A2, A2/A2 genotypes) or absence (A1/A1 genotype) of HLA-A2. A two-way analysis of variance was used to assess the effect of the HLA-A2 allele on age at onset of dementia. No association between HLA-A2 and APOE-4 was found, and the presence of HLA-A2 allele did not increase AD risk. There was also no evidence for an association between HLA-A2 and earlier onset age of AD. Examination age, sex, family history of AD, and recruitment site had no influence on these results. In conclusion, the HLA-A2 allele did not influence AD risk or onset age in this study population. A2 heterozygosity, and population differences, including stratification sub- structures, and other undetermined factors could contribute to discrepant findings among studies.

AB - The apolipoprotein E (APOE)-4 allele is a major risk factor for late- onset Alzheimer disease (AD), but it does not account for all the genetic variation in late-onset AD; thus, other genetic markers must be examined. Previous studies suggest an HLA-A2 allele association with risk and earlier onset age of AD. Because these effects may be additive to those of APOE-4, we studied HLA-A2 and APOE-4 frequencies in AD patients and cognitively intact controls. A total of 712 unrelated Caucasian subjects included 479 patients with AD (435 sporadic, 44 familial) and 233 controls. Patients (mean ± SD age 73.9 ± 7.9 years, range 42-93 years) had probable AD, according to standard diagnostic criteria; controls (mean ± SD age 70.4 ± 8.5 years, range 37-92 years) were cognitively intact. APOE and HLA-A2 typing used polymerase chain reaction to indicate the number of APOE-4 alleles present as well as the presence (A1/A2, A2/A2 genotypes) or absence (A1/A1 genotype) of HLA-A2. A two-way analysis of variance was used to assess the effect of the HLA-A2 allele on age at onset of dementia. No association between HLA-A2 and APOE-4 was found, and the presence of HLA-A2 allele did not increase AD risk. There was also no evidence for an association between HLA-A2 and earlier onset age of AD. Examination age, sex, family history of AD, and recruitment site had no influence on these results. In conclusion, the HLA-A2 allele did not influence AD risk or onset age in this study population. A2 heterozygosity, and population differences, including stratification sub- structures, and other undetermined factors could contribute to discrepant findings among studies.

KW - Alzheimer disease

KW - Apolipoprotein E

KW - HLA

UR - http://www.scopus.com/inward/record.url?scp=0032849038&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032849038&partnerID=8YFLogxK

U2 - 10.1007/s100480050080

DO - 10.1007/s100480050080

M3 - Article

VL - 2

SP - 177

EP - 182

JO - Neurogenetics

JF - Neurogenetics

SN - 1364-6745

IS - 3

ER -