The Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians: Vitamin D receptor polymorphisms and plasma renin activity
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OBJECTIVES: 25-Hydroxyvitamin D (25(OH)D) deficiency and excess activity of the renin-angiotensin system (RAS) are both associated with cardiovascular disease. Vitamin D interacts with the vitamin D receptor (VDR) to negatively regulate renin expression in mice; however, human studies linking genetic variation in the VDR with renin are lacking. We evaluated (i) whether genetic variation in the VDR at the Fok1 polymorphism was associated with plasma renin activity (PRA) in a population of hypertensives and a separate population of normotensives and (ii) whether the association between Fok1 genotype and PRA was independent of 25(OH)D levels. DESIGN/PATIENTS/MEASUREMENTS: Genetic association study, assuming an additive model of inheritance, of 375 hypertensive and 146 normotensive individuals from the HyperPATH cohort, who had PRA assessments after 1 week of high dietary sodium balance (HS) and l week of low dietary sodium balance (LS). RESULTS: The minor allele (T) at the Fok1 polymorphism was significantly associated with lower PRA in hypertensives (LS: β = -0·22, P < 0·01; HS: β = -0·19, P < 0·01); when repeated in normotensives, a similar relationship was observed (LS: β = -0·17, P < 0·05; HS: β = -0·18, P = 0·14). In multivariable analyses, both higher 25(OH)D levels and the T allele at Fok1 were independently associated with lower PRA in hypertensives; however, 25(OH)D was not associated with PRA in normotensives. CONCLUSIONS: Genetic variation at the Fok1 polymorphism of the VDR gene, in combination with 25(OH)D levels, was associated with PRA in hypertension. These findings support the vitamin D-VDR complex as a potential regulator of renin activity in humans.
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- Authors
- Vaidya, A., Sun, B., Forman, J. P., Hopkins, P. N., Brown, N. J., Kolatkar, N. S., Williams, G. H., & Williams, J. S.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Utah (US)
- Vanderbilt University Medical Center (US)
- Genentech (US)
- Corresponding author
- Vaidya, Anand
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2011-05-06
- Volume
- 74
- Issue
- 6
- Pages
- 783-790
- ISSN
- 0300-0664 (ISSN-L)
- PMC
- PMC3089671
- OpenAlex
- W1549074775
- Cited by
- 58
- References
- 37
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 10
- FWCI
- 5.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Vanderbilt University
- University of Utah
- National Heart, Lung, and Blood Institute (K23HL08236-03, F32HL104776, T32HL007609, K08HL079929, P50HL055000, K23HL111771)
- U.S. National Library of Medicine (U54LM008748)
- National Center for Research Resources (M01 RR 02635, UL1RR025758, M01RR002635)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- vitamin D receptor, Fok1 polymorphism, plasma renin activity, 25-hydroxyvitamin D, hypertension, renin-angiotensin system, genetic association, dietary sodium, cardiovascular disease, Caucasians
- MeSH terms
- Adult, Blood Pressure, Cross-Sectional Studies, Female, Gene Frequency, Genotype, Humans, Hypertension, Male, Middle Aged, Renin, Vitamin D, Linkage Disequilibrium, Linear Models, Sodium Chloride, Dietary, Receptors, Calcitriol, Polymorphism, Single Nucleotide, White People
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