Apolipoprotein E genotype and mortality: findings from the Cache County Study.
OBJECTIVE
To evaluate the association between apolipoprotein E (apo E) epsilon4 and mortality, the population attributable risk for mortality with epsilon4, and relative contributions of cardiovascular disease (CVD) and Alzheimer's disease (AD).


METHODS
Population-based cohort study.


METHODS
Community-based.


METHODS
Permanent residents of Cache County, Utah, aged 65 and older as of January 1, 1995.


METHODS
Participants were genotyped at the apo E locus using buccal-swab deoxyribonucleic acid. Cardiovascular health was ascertained using self- or proxy-report interviews at participants' residences. AD was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders criteria. Utah Department of Vital Statistics quarterly reports were reviewed to identify participants who died.


RESULTS
Crude evaluations showed nonsignificantly greater risk of death for epsilon2/2 (hazard ratio (HR)=1.66, 95% confidence interval (CI)=0.92-2.76) and epsilon3/4 (HR=1.11, 95% CI=0.97-1.26) genotypes and significantly greater risk for epsilon4/4 (HR=1.48, 95% CI=1.09-1.96). After adjustment for age, age(2), sex, and education, risks increased to 1.98 (95% CI=1.08-3.35), 1.28 (95% CI=1.12-1.46), and 2.02 (95% CI=1.47-2.71), respectively, compared with epsilon3/3 genotypes. Adjustment for presence of any CVD did not change the risk of death for epsilon3/4 and epsilon4/4. Adjustment for AD reduced the risk of death for epsilon3/4 (HR=1.13, 95% CI=0.99-1.30) and epsilon4/4 (HR=1.59, 95% CI=1.15-2.14). The population attributable risk of death for epsilon3/4 and epsilon4/4 genotypes combined is estimated at 9.6%.


CONCLUSIONS
These findings suggested that the epsilon2/2, epsilon3/4, and epsilon4/4 genotypes have greater early mortality risks. Further analyses showed that AD partially mediates the association between epsilon3/4, epsilon4/4, and death.
Hayden
Kathleen M
KM
Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina.
Zandi
Peter P
PP
Lyketsos
Constantine G
CG
Tschanz
JoAnn T
JT
Norton
Maria C
MC
Khachaturian
Ara S
AS
Pieper
Carl F
CF
Welsh-Bohmer
Kathleen A
KA
Breitner
John C S
JC
D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000401:mortality*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000401:mortality*; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D015995:Prevalence; D012307:Risk Factors; D017678:Sex Distribution; D016019:Survival Analysis; D014589:Utah / Q000453:epidemiology
D053327:Apolipoprotein E4; D001057:Apolipoproteins E