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 ε4 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.

Figure 1. Plot of WHICAP participants by AIMs-defined ancestry versus HapMap populations

WHICAP participants Yellow: Predominantly Caucasian AIMs-defined ancestry Green: Admixed/Hispanic AIMs-defined ancestry Blue: Predominantly African AIMs-defined ancestry HapMap populations Light Brown: Ancestrally homogenous Caucasian population (CEPH) Light Blue: Ancestrally homogenous Yoruban Black population (YRI) Red: Ancestrally homogenous East Asian population (CHJA)