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Aromatase variants modify risk for Alzheimer's disease in a multiethnic female cohort.

ABSTRACT: BACKGROUND/AIMS:Few studies of gene variants that affect estrogen activity investigate their association with risk for Alzheimer's disease (AD) in women of different ethnicities. We investigated the influence of CYP19 polymorphisms on risk for AD in a multiethnic cohort of women, with individual ethnicity assessed by genetic population ancestry informative markers (AIMs) as well as by self-identified ethnicity. METHODS:Among 1,686 women participating in the Washington Heights Inwood Columbia Aging Project, association with risk for AD was assessed for 41 single nucleotide polymorphisms (SNPs) on the CYP19 gene using multivariable logistic regression, adjusting for age, presence of an APOE ?4 allele, years of education, and body mass index. RESULTS:Risk for AD was associated with 6 SNPs in women of predominantly Caucasian AIMs-defined ancestry. Of these, 2 were also associated with decreased risk of AD in women of admixed/Hispanic AIMs ancestry. Two separate SNPs were found to be protective in women of predominantly African AIMs-based ancestry. CONCLUSIONS:CYP19 polymorphisms affect risk for AD in women, and risk alleles vary by AIMs-defined ancestry. These effects are possibly due to linkage disequilibrium patterns or differences in the prevalence of comorbid risk factors mediating the SNP effect on risk for AD by group.

SUBMITTER: Janicki SC

PROVIDER: S-EPMC4036496 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Aromatase variants modify risk for Alzheimer's disease in a multiethnic female cohort.

Janicki S C SC Park N N Cheng R R Schupf N N Clark L N LN Lee J H JH

Dementia and geriatric cognitive disorders 20130418 5-6

<h4>Background/aims</h4>Few studies of gene variants that affect estrogen activity investigate their association with risk for Alzheimer's disease (AD) in women of different ethnicities. We investigated the influence of CYP19 polymorphisms on risk for AD in a multiethnic cohort of women, with individual ethnicity assessed by genetic population ancestry informative markers (AIMs) as well as by self-identified ethnicity.<h4>Methods</h4>Among 1,686 women participating in the Washington Heights Inwo ...[more]

PMID: 23635391

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Project description:Background and Objectives:Clinic-based studies of patients with Alzheimer's disease (AD) have demonstrated the value of assessing dependence when characterizing patients' functional status. The Dependence Scale, a validated tool to assess level of caregiving needs, is associated with markers of disease severity, cost, and progression, while offering independent functional information about patients. This study examines whether such associations between the Dependence Scale and markers of disease severity demonstrated in clinical cohorts are similarly exhibited in a multiethnic community population of individuals with AD. Research Design and Methods:One hundred fifty four elders with AD enrolled in the Predictors 3 cohort were assessed with the Dependence Scale, modified Mini-Mental State Examination (mMMS), instrumental (IADL) and basic (BADL) activities of daily living, and Clinical Dementia Rating (CDR) Scale, and were assigned an Equivalent Institutional Care (EIC) rating. Cross-sectional associations were examined using bivariate correlations and one-way analysis of variance analyses. Fisher-z tests examined differences in strengths of associations across previous clinic and current community cohorts. Results:Dependence Scale scores were associated with CDR (r = .20, p = .013), mMMS (r = -.23, p = .005), IADL (r = .39, p < .001), BADL (r = .65, p < .001), and EIC (r = .51, p < .001). Dependence was unassociated with ethnicity (F[3,144] = 1.027, p = .3822), age (r = .120, p = .145), and education (r = -.053, p = .519). The strength of the correlations was comparable across cohorts except that BADLs were more strongly associated with dependence (z = -4.60, p < .001) in the community cohort, and living arrangement was not associated with dependence (r = .13, p = .130). Discussion and Implications:Associations between the Dependence Scale and markers of disease severity in a clinic-based cohort of AD patients are similar to associations in a multiethnic community cohort of individuals diagnosed with AD. The Dependence Scale relates to markers of disease severity rather than demographic factors, and may offer an unbiased assessment of care required in multiethnic and community populations.

Dataset Information

Aromatase variants modify risk for Alzheimer's disease in a multiethnic female cohort.

Publications

Aromatase variants modify risk for Alzheimer's disease in a multiethnic female cohort.

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