Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics

Hana Koutnikova, Markku Laakso, Lu Lu, Roy Combe, Jussi Paananen, Teemu Kuulasmaa, Johanna Kuusisto, Hans Ulrich Häring, Torben Hansen, Oluf Pedersen, Ulf Smith, Markolf Hanefeld, Robert Williams, Johan Auwerx

Research output: Contribution to journalArticle

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Abstract

Hypertension is a major health problem of largely unknown genetic origins. To identify new genes responsible for hypertension, genetic analysis of recombinant inbred strains of mice followed by human association studies might prove powerful and was exploited in our current study. Using a set of 27 recombinant BXD strains of mice we identified a quantitative trait locus (QTL) for blood pressure (BP) on distal chromosome 9. The association analysis of markers encompassing the syntenic region on human chromosome 3 gave in an additive genetic model the strongest association for rs17030583 C/T and rs2291897 G/A, located within the UBP1 locus, with systolic and diastolic BP (rs17030583: 1.3±0.4 mmHg p<0.001, 0.8±0.3 mmHg p = 0.006, respectively and rs2291897: 1.5±0.4 mmHg p<0.001, 0.8±0.3 mmHg p = 0.003, respectively) in three separate studies. Our study, which underscores the marked complementarities of mouse and human genetic approaches, identifies the UBP1 locus as a critical blood pressure determinant. UBP1 plays a role in cholesterol and steroid metabolism via the transcriptional activation of CYP11A, the rate-limiting enzyme in pregnenolone and aldosterone biosynthesis. We suggest that UBP1 and its functional partners are components of a network controlling blood pressure.

Original languageEnglish (US)
Article numbere1000591
JournalPLoS genetics
Volume5
Issue number8
DOIs
StatePublished - Aug 1 2009

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Medical Genetics
blood pressure
blood
Blood Pressure
hypertension
loci
mice
steroid metabolism
pregnenolone
chromosomes
chromosome
cholesterol metabolism
aldosterone
diastolic blood pressure
systolic blood pressure
transcriptional activation
genetic techniques and protocols
quantitative trait loci
complementarity
Hypertension

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics. / Koutnikova, Hana; Laakso, Markku; Lu, Lu; Combe, Roy; Paananen, Jussi; Kuulasmaa, Teemu; Kuusisto, Johanna; Häring, Hans Ulrich; Hansen, Torben; Pedersen, Oluf; Smith, Ulf; Hanefeld, Markolf; Williams, Robert; Auwerx, Johan.

In: PLoS genetics, Vol. 5, No. 8, e1000591, 01.08.2009.

Research output: Contribution to journalArticle

Koutnikova, H, Laakso, M, Lu, L, Combe, R, Paananen, J, Kuulasmaa, T, Kuusisto, J, Häring, HU, Hansen, T, Pedersen, O, Smith, U, Hanefeld, M, Williams, R & Auwerx, J 2009, 'Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics', PLoS genetics, vol. 5, no. 8, e1000591. https://doi.org/10.1371/journal.pgen.1000591
Koutnikova, Hana ; Laakso, Markku ; Lu, Lu ; Combe, Roy ; Paananen, Jussi ; Kuulasmaa, Teemu ; Kuusisto, Johanna ; Häring, Hans Ulrich ; Hansen, Torben ; Pedersen, Oluf ; Smith, Ulf ; Hanefeld, Markolf ; Williams, Robert ; Auwerx, Johan. / Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics. In: PLoS genetics. 2009 ; Vol. 5, No. 8.
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