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Common Polymorphisms in the CYP11B1 and CYP11B2 Genes: Evidence for a Digenic Influence on Hypertension

Alvarez-Madrazo, Samantha ; MacKenzie, Scott M. ; Davies, Eleanor ; Fraser, Robert ; Lee, Wai-Kwong ; Brown, Morris ; Caulfield, Mark J. ; Dominiczak, Anna F. ; Farrall, Martin and Lathrop, Mark , et al. (2013) In Hypertension 61(1). p.232-239
Abstract
The locus encompassing the corticosteroidogenic genes CYP11B2 and CYP11B1 is of potential importance in essential hypertension. We analyzed the association of polymorphisms at this locus with risk of essential hypertension, using 2 white case-control collections for discovery (n = 3340) and confirmation (n = 2929). Single-marker and haplotype analyses were performed, with the CYP11B2 Intron 2 Conversion polymorphism showing strongest association with hypertension in both cohorts and in combined analysis (odds ratio = 1.16, P = 8.54x10(-5)). The CYP11B1 ACA haplotype associated with increased risk of hypertension relative to the alternative, GTC (odds ratio = 1.11; P = 7.4x10(-3)), whereas the CYP11B2 TWtC haplotype seemed protective... (More)
The locus encompassing the corticosteroidogenic genes CYP11B2 and CYP11B1 is of potential importance in essential hypertension. We analyzed the association of polymorphisms at this locus with risk of essential hypertension, using 2 white case-control collections for discovery (n = 3340) and confirmation (n = 2929). Single-marker and haplotype analyses were performed, with the CYP11B2 Intron 2 Conversion polymorphism showing strongest association with hypertension in both cohorts and in combined analysis (odds ratio = 1.16, P = 8.54x10(-5)). The CYP11B1 ACA haplotype associated with increased risk of hypertension relative to the alternative, GTC (odds ratio = 1.11; P = 7.4x10(-3)), whereas the CYP11B2 TWtC haplotype seemed protective relative to the contrasting CConvT (odds ratio = 0.88, P = 2.2x10(-3)). Analysis spanning the whole CYP11B1/CYP11B2 locus showed that haplotypes associated with raised risk of hypertension tend to coexist. Functional analysis of heterozygous human adrenal tissue demonstrated decreased CYP11B2 expression and increased CYP11B1 expression for those alleles associating with reduced risk of hypertension. These results confirm the hypertensive influence of this locus, with data suggesting a complex digenic mechanism whereby altered relative CYP11B1 and CYP11B2 gene expression could have a chronic effect on enzyme activity and corticosteroid synthesis. (Hypertension. 2013;61:232-239.). center dot Online Data Supplement (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
hypertension, aldosterone, cortisol, CYP11B1, CYP11B2, haplotypes, population
in
Hypertension
volume
61
issue
1
pages
232 - 239
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000312386200042
  • scopus:84871620553
ISSN
1524-4563
DOI
10.1161/HYPERTENSIONAHA.112.200741
language
English
LU publication?
yes
id
afae6f2f-61c5-446c-a127-935e8274ad53 (old id 3400727)
date added to LUP
2016-04-01 11:14:33
date last changed
2024-01-07 11:06:35
@article{afae6f2f-61c5-446c-a127-935e8274ad53,
  abstract     = {{The locus encompassing the corticosteroidogenic genes CYP11B2 and CYP11B1 is of potential importance in essential hypertension. We analyzed the association of polymorphisms at this locus with risk of essential hypertension, using 2 white case-control collections for discovery (n = 3340) and confirmation (n = 2929). Single-marker and haplotype analyses were performed, with the CYP11B2 Intron 2 Conversion polymorphism showing strongest association with hypertension in both cohorts and in combined analysis (odds ratio = 1.16, P = 8.54x10(-5)). The CYP11B1 ACA haplotype associated with increased risk of hypertension relative to the alternative, GTC (odds ratio = 1.11; P = 7.4x10(-3)), whereas the CYP11B2 TWtC haplotype seemed protective relative to the contrasting CConvT (odds ratio = 0.88, P = 2.2x10(-3)). Analysis spanning the whole CYP11B1/CYP11B2 locus showed that haplotypes associated with raised risk of hypertension tend to coexist. Functional analysis of heterozygous human adrenal tissue demonstrated decreased CYP11B2 expression and increased CYP11B1 expression for those alleles associating with reduced risk of hypertension. These results confirm the hypertensive influence of this locus, with data suggesting a complex digenic mechanism whereby altered relative CYP11B1 and CYP11B2 gene expression could have a chronic effect on enzyme activity and corticosteroid synthesis. (Hypertension. 2013;61:232-239.). center dot Online Data Supplement}},
  author       = {{Alvarez-Madrazo, Samantha and MacKenzie, Scott M. and Davies, Eleanor and Fraser, Robert and Lee, Wai-Kwong and Brown, Morris and Caulfield, Mark J. and Dominiczak, Anna F. and Farrall, Martin and Lathrop, Mark and Hedner, Thomas and Melander, Olle and Munroe, Patricia B. and Samani, Nilesh and Stewart, Paul M. and Wahlstrand, Bjorn and Webster, John and Palmer, Colin N. A. and Padmanabhan, Sandosh and Connell, John M.}},
  issn         = {{1524-4563}},
  keywords     = {{hypertension; aldosterone; cortisol; CYP11B1; CYP11B2; haplotypes; population}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{232--239}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Hypertension}},
  title        = {{Common Polymorphisms in the CYP11B1 and CYP11B2 Genes: Evidence for a Digenic Influence on Hypertension}},
  url          = {{http://dx.doi.org/10.1161/HYPERTENSIONAHA.112.200741}},
  doi          = {{10.1161/HYPERTENSIONAHA.112.200741}},
  volume       = {{61}},
  year         = {{2013}},
}