Estrogen Receptor Variants Modify Risk for Alzheimer's Disease in a Multiethnic Female Cohort (P07.159)

Abstract

Objective: Genetic variants that affect estrogen activity may influence risk for Alzheimer9s disease (AD). We investigated the influence of ESR2 polymorphisms on risk for AD in a multiethnic cohort of women, and hypothesized that gene variants would affect risk for AD differently in populations of different genetic ancestry or self-defined ethnicity. Background Most previous studies which have demonstrated an association between AD and ESR2 polymorphisms have been conducted in Caucasians. Few polymorphisms have been assessed in a multiethnic cohort in which members have been evaluated in a consistent manner. We examined the relationship between ESR2 polymorphisms and risk for AD in a multiethnic community of elderly women, with individual ancestry assessed by both genetic population ancestry markers and self - identified ethnicity. Design/Methods: 1686 women participating in the Washington Heights Inwood Columbia Aging Project (WHICAP), were followed at 18 - 24 month intervals. AD diagnosis was the primary outcome and was based on data from standardized neurological examinations and neuropsychological batteries. DNA was genotyped for 20 ESR2 single-nucleotide polymorphisms (SNPs). We used multivariable logistic regression to estimate likelihood of AD by SNP genotype, adjusting for age, presence of an APOE e4 allele, body mass index, history of diabetes mellitus, and current smoking. Analyses were first conducted stratifying by models of population-based genetic ancestry based on a set of 100 genetically conserved SNPs, and then by self -reported ethnicity. Results: Increased risk for AD was associated with four ESR2 SNPs in women of predominantly Caucasian genetic ancestry: rs944045, rs1256062, rs10144225, and rs2274705. Additionally, rs10137185 was associated with decreased risk for AD in women who defined themselves as Black, and demonstrated a trend towards significance in women of predominantly African genetic ancestry. Conclusions: Our findings suggest that ESR2 polymorphisms in women play a role in risk for AD which varies by genetic population ancestry or ethnicity. Supported by: Alzheimer9s Association IIRG-08-90655,Genetics of Estrogen and Alzheimer9s Disease in a Multiethnic Cohort, NIH 5-T32MH020004-10 and the Charles and Ann Lee Saunders Brown Fellowship Fund. Disclosure: Dr. Janicki has nothing to disclose. Dr. Park has nothing to disclose. Dr. Cheng has nothing to disclose. Dr. Lee has nothing to disclose. Dr. Schupf has nothing to disclose. Dr. Clark has nothing to disclose.