Apolipoprotein E : risk factor for Alzheimer disease

• Published in: American journal of human genetics Vol. 54; no. 4; pp. 643 - 649
• Main Authors: TSAI, M.-S, TANGALOS, E. G, PETERSEN, R. C, SMITH, G. E, SCHAID, D. J, KOKMEN, E, IVNIK, R. J, THIBODEAU, S. N
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01.04.1994
• Subjects: Age of Onset; Aged; Aged, 80 and over; Alleles; Alzheimer Disease - genetics; Alzheimer's disease; apolipoprotein E; Apolipoprotein E4; APOLIPOPROTEINS; Apolipoproteins E - genetics; Base Sequence; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; Case-Control Studies; CENTRAL NERVOUS SYSTEM; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DISEASES; Female; Gene Frequency; GENE MUTATIONS; Genes; GENETIC MAPPING; Genetic Predisposition to Disease; genotypes; Heterozygote; Homozygote; Humans; LIPIDS; LIPOPROTEINS; Logistic Models; Male; man; MAPPING; Medical sciences; Molecular Sequence Data; MUTATIONS; NERVOUS SYSTEM; NERVOUS SYSTEM DISEASES; Neurology; Odds Ratio; ORGANIC COMPOUNDS; PROTEINS 550400 > Genetics; Risk Factors; risks; Sequence Analysis, DNA; Human; Nervous system diseases; Late; Genetic inheritance; Alzheimer disease; Genotype; Apolipoproteins; Cerebral disorder; Allele; Age of onset; Central nervous system disease; Risk factor; Degenerative disease
• ISSN: 0002-9297; 1537-6605

The apolipoprotein E gene (APOE) has three common alleles (epsilon 2, epsilon 3, and epsilon 4) that determine six genotypes in the general population. In this study, we examined 77 patients with late-onset Alzheimer disease (AD), along with an equal number of age- and sex-matched controls, for an association with the APOE-epsilon 4 allele. We show that the frequency of this allele among AD patients was significantly higher than that among the control population (.351 vs. .130, P = .000006). The genotype frequencies also differed between the two groups (P = .0002), with the APOE-epsilon 4/epsilon 3 genotype being the most common in the AD group and the APOE-epsilon 3/epsilon 3 being the most common in the control group. In the AD group, homozygosity for epsilon 4 was found in nine individuals, whereas none was found in the control group. The odds ratio for AD, when associated with one or two epsilon 4 alleles, was 4.6 (95% confidence interval [CI] 1.9-12.3), while the odds ratio for AD, when associated with heterozygosity for APOE-epsilon 4, was 3.6 (95% CI 1.5-9.8). Finally, the median age at onset among the AD patients decreased from 83 to 78 to 74 years as the number of APOE-epsilon 4 alleles increased from 0 to 1 to 2, respectively (test for trend, P = .001). Our data, which are in agreement with recent reports, suggest that the APOE-epsilon 4 allele is associated with AD and that this allelic variant may be an important risk factor for susceptibility to AD in the general population.