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.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, the Neuropsychiatric Institute, the Alzheimer's Disease Center, and the Center on Aging, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Small
authors.forename: W K
authors.initials: WK
authors.lastname: Scott
authors.forename: S
authors.initials: S
authors.lastname: Komo
authors.forename: L H
authors.initials: LH
authors.lastname: Yamaoka
authors.forename: L A
authors.initials: LA
authors.lastname: Farrer
authors.forename: S H
authors.initials: SH
authors.lastname: Auerbach
authors.forename: A M
authors.initials: AM
authors.lastname: Saunders
authors.forename: A D
authors.initials: AD
authors.lastname: Roses
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D015789:HLA-A2 Antigen / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D015789:HLA-A2 Antigen