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

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18 Scopus citations

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

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Keywords

  • Alzheimer disease
  • Apolipoprotein E
  • HLA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

Cite this

Small, G. W., Scott, W. K., Komo, S., Yamaoka, L. H., Farrer, L. A., Auerbach, S. H., Saunders, A. M., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1999). No association between the HLA-A2 allele and Alzheimer disease. Neurogenetics, 2(3), 177-182. https://doi.org/10.1007/s100480050080