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Apolipoprotein E genotype and mortality: findings from the Cache County Study.

Abstract

OBJECTIVES

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).

DESIGN

Population-based cohort study.

SETTING

Community-based.

PARTICIPANTS

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

MEASUREMENTS

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%.

CONCLUSION

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.

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  • Authors+Show Affiliations

    ,

    Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina.

    , , , , , , , ,

    Source

    MeSH

    Age Distribution
    Aged
    Aged, 80 and over
    Alzheimer Disease
    Apolipoprotein E4
    Apolipoproteins E
    Cardiovascular Diseases
    Cohort Studies
    Confidence Intervals
    Female
    Follow-Up Studies
    Gene Frequency
    Genetics, Population
    Genotype
    Humans
    Longitudinal Studies
    Male
    Prevalence
    Risk Factors
    Sex Distribution
    Survival Analysis
    Utah

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    15935014

    Citation

    Hayden, Kathleen M., et al. "Apolipoprotein E Genotype and Mortality: Findings From the Cache County Study." Journal of the American Geriatrics Society, vol. 53, no. 6, 2005, pp. 935-42.
    Hayden KM, Zandi PP, Lyketsos CG, et al. Apolipoprotein E genotype and mortality: findings from the Cache County Study. J Am Geriatr Soc. 2005;53(6):935-42.
    Hayden, K. M., Zandi, P. P., Lyketsos, C. G., Tschanz, J. T., Norton, M. C., Khachaturian, A. S., ... Breitner, J. C. (2005). Apolipoprotein E genotype and mortality: findings from the Cache County Study. Journal of the American Geriatrics Society, 53(6), pp. 935-42.
    Hayden KM, et al. Apolipoprotein E Genotype and Mortality: Findings From the Cache County Study. J Am Geriatr Soc. 2005;53(6):935-42. PubMed PMID: 15935014.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Apolipoprotein E genotype and mortality: findings from the Cache County Study. AU - Hayden,Kathleen M, AU - Zandi,Peter P, AU - Lyketsos,Constantine G, AU - Tschanz,JoAnn T, AU - Norton,Maria C, AU - Khachaturian,Ara S, AU - Pieper,Carl F, AU - Welsh-Bohmer,Kathleen A, AU - Breitner,John C S, AU - ,, PY - 2005/6/7/pubmed PY - 2005/8/17/medline PY - 2005/6/7/entrez SP - 935 EP - 42 JF - Journal of the American Geriatrics Society JO - J Am Geriatr Soc VL - 53 IS - 6 N2 - OBJECTIVES: 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). DESIGN: Population-based cohort study. SETTING: Community-based. PARTICIPANTS: Permanent residents of Cache County, Utah, aged 65 and older as of January 1, 1995. MEASUREMENTS: 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%. CONCLUSION: 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. SN - 0002-8614 UR - https://www.unboundmedicine.com/medline/citation/15935014/Apolipoprotein_E_genotype_and_mortality:_findings_from_the_Cache_County_Study_ L2 - https://doi.org/10.1111/j.1532-5415.2005.53301.x DB - PRIME DP - Unbound Medicine ER -