Common polymorphisms in the CYP11B1 and CYP11B2 genes: evidence for a digenic influence on hypertension

Samantha Alvarez-Madrazo, Scott M Mackenzie, Eleanor Davies, Robert Fraser, Wai-Kwong Lee, Morris Brown, Mark J Caulfield, Anna F Dominiczak, Martin Farrall, Mark Lathrop, Thomas Hedner, Olle Melander, Patricia B Munroe, Nilesh Samani, Paul M Stewart, Björn Wahlstrand, John Webster, Colin N A Palmer, Sandosh Padmanabhan, John M Connell

    Research output: Contribution to journalArticlepeer-review

    30 Citations (Scopus)


    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=8.54×10(-5)). The CYP11B1 ACA haplotype associated with increased risk of hypertension relative to the alternative, GTC (odds ratio=1.11; P=7.4×10(-3)), whereas the CYP11B2 TWtC haplotype seemed protective relative to the contrasting CConvT (odds ratio=0.88, P=2.2×10(-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.

    Original languageEnglish
    Pages (from-to)232-239
    Number of pages8
    Issue number1
    Early online date12 Nov 2012
    Publication statusPublished - Jan 2013


    • adolescent
    • adrenal glands
    • adult
    • aged
    • aldosterone synthase
    • alleles
    • case-control studies
    • female
    • gene frequency
    • genetic association studies
    • genotype
    • haplotypes
    • humans
    • hypertension
    • male
    • middle aged
    • polymorphism, single nucleotide
    • steroid 11-beta-Hydroxylase
    • aldosterone
    • cortisol
    • CYP11B1
    • CYP11B2
    • population


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