Variants in CYP17 and CYP19 Cytochrome P450 Genes are Associated with Onset of Alzheimer’s Disease in Women with Down Syndrome
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CYP17 and CYP19 are involved in the peripheral synthesis of estrogens, and polymorphisms in CYP17 and CYP19 have been associated with increased risk of estrogen-related disorders. Women with Down syndrome (DS) have early onset and high risk for Alzheimer's disease (AD). We conducted a prospective community-based cohort study to examine the relationship between SNPs in CYP17 and CYP19 and cumulative incidence of AD, hormone levels and sex hormone binding globulin in women with DS. Two hundred and thirty-five women with DS, 31 to 67 years of age and nondemented at initial examination, were assessed for cognitive and functional abilities, behavioral/psychiatric conditions, and health status at 14-20 month intervals over five assessment cycles. We genotyped these individuals for single-nucleotide polymorphisms (SNPs) in CYP17 and CYP19. Four SNPs in CYP17 were associated with a two and one half-fold increased risk of AD, independent of APOE genotype. Four SNPs in CYP19 were associated with a two-fold increased risk of AD, although three were significant only in those without an APOE ε4 allele. Further, carrying high risk alleles in both CYP17 and CYP19 was associated with an almost four-fold increased risk of AD (OR = 3.8, 95% CI, 1.6-9.5) and elevated sex hormone binding globulin in postmenopausal women. The main effect of the CYP17 and CYP19 variants was to decrease the age at onset. These findings suggest that genes contributing to estrogen bioavailability influence risk of AD in women with DS.
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The presence of high-risk alleles in both CYP17 and CYP19 increases the risk of AD in menopausal women by almost four times.
“In addition, the presence of high-risk alleles in both CYP17 and CYP19 increased the risk of AD in menopausal women by almost four times [23,24].”
From Effect of Caffeine Consumption on the Risk for Neurological and Psychiatric Disorders: Sex Differences in Human (2020) · cites this paper as [23]
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- Authors
- Chace, C., Pang, D., Weng, C., Temkin, A., Lax, S., Silverman, W., Zigman, W., Ferin, M., Lee, J. H., Tycko, B., & Schupf, N.
- Affiliations
- Columbia University Irving Medical Center (US)
- Kennedy Krieger Institute (US)
- Department of Psychology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA
- Corresponding author
- Schupf, Nicole
- ORCID
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2012-02-07
- Volume
- 28
- Issue
- 3
- Pages
- 601-612
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC3276705
- OpenAlex
- W1802303241
- Cited by
- 53
- References
- 60
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 4 · 2014: 4 · 2013: 4 · 2012: 2
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Office for People With Developmental Disabilities
- National Institute on Aging (R01AG014673, P50AG008702, AG014673)
- National Institute of Mental Health (R01MH084995)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD035897, HD035897, U54HD079123)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, Down syndrome
- MeSH terms
- Adult, Aged, Alzheimer Disease, Aromatase, Disability Evaluation, Down Syndrome, Female, Gene Frequency, Genotype, Humans, Menopause, Middle Aged, Psychiatric Status Rating Scales, Radioimmunoassay, Sex Hormone-Binding Globulin, Steroid 17-alpha-Hydroxylase, Cohort Studies, Proportional Hazards Models, Age of Onset, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Apolipoprotein E4
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