No association between the HLA-A2 allele and Alzheimer disease.
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.
Small
G W
GW
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.
Scott
W K
WK
Komo
S
S
Yamaoka
L H
LH
Farrer
L A
LA
Auerbach
S H
SH
Saunders
A M
AM
Roses
A D
AD
Haines
J L
JL
Pericak-Vance
M A
MA
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
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D015789:HLA-A2 Antigen