Journal
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
Volume 65, Issue 2, Pages 332-339Publisher
WILEY
DOI: 10.1111/jgs.14537
Keywords
polymorphisms; estrogen metabolic pathway; Alzheimer's disease
Categories
Ask authors/readers for more resources
OBJECTIVES: To investigate whether genetic variations on the estrogen metabolic pathway would be associated with risk of Alzheimer's disease (AD). DESIGN: Cross-sectional study. SETTING: Individuals were recruited at the Memory Clinic, Queen Mary Hospital, Hong Kong. PARTICIPANTS: Chinese individuals with (n = 426) and without (n = 350) AD. MEASUREMENTS: All subjects underwent a standardized cognitive assessment and genotyping of four candidate genes on the estrogen metabolic pathway (estrogen receptor a gene (ESR1), estrogen receptor b gene (ESR2), cytochrome P450 19A1 gene (CYP19A1), cytochrome P450 11A1 gene (CYP11A1)). RESULTS: Apart from consistent results showing an association between apolipoprotein (APO) E and AD, strong evidence of disease associations were found for polymorphisms in ESR2 and CYP11A1 based on the entire data set. For ESR2, significant protective effects were found for A alleles of rs4986938 (permuted P =.02) and rs867443 (permuted P =.02). For CYP11A1, significant risk effects were found for G alleles of rs11638442 (permuted P =.03) and rs11632698 (permuted P =.03). Stratifying subjects according to APOE e4 status, their genetic effects continued to be significant in the APOE e4-negative subgroup. Associations between CYP11A1 polymorphisms (rs2279357, rs2073475) and risk of AD were detected in women but not men. Further gene-level analysis confirmed the above association between ESR2 and CYP11A1, and pathway-level analysis highlighted the genetic effect of the estrogen metabolic pathway on disease susceptibility (permuted pathway-level P =.03). CONCLUSION: Consistent with previous biological findings for sex steroid hormones in the central nervous system, genetic alterations on the estrogen metabolic pathway were revealed in the Chinese population. Confirmation of these present findings in an independent population is warranted to elucidate disease pathogenesis and to explore the potential of hormone therapy in the treatment of AD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available