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

Research output: Contribution to journal › Journal article › Research › peer-review

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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 W; Auwerx, Johan.

In: PLoS Genetics, Vol. 5, No. 8, 2009, p. e1000591.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Koutnikova, H, Laakso, M, Lu, L, Combe, R, Paananen, J, Kuulasmaa, T, Kuusisto, J, Häring, H-U, Hansen, T, Pedersen, O, Smith, U, Hanefeld, M, Williams, RW & 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, pp. e1000591. https://doi.org/10.1371/journal.pgen.1000591

APA

Koutnikova, H., Laakso, M., Lu, L., Combe, R., Paananen, J., Kuulasmaa, T., Kuusisto, J., Häring, H-U., Hansen, T., Pedersen, O., Smith, U., Hanefeld, M., Williams, R. W., & Auwerx, J. (2009). Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics. PLoS Genetics, 5(8), e1000591. https://doi.org/10.1371/journal.pgen.1000591

Vancouver

Koutnikova H, Laakso M, Lu L, Combe R, Paananen J, Kuulasmaa T et al. Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics. PLoS Genetics. 2009;5(8):e1000591. https://doi.org/10.1371/journal.pgen.1000591

Author

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 W ; 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. pp. e1000591.

Bibtex

@article{6d685ff035af11df8ed1000ea68e967b,
title = "Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics",
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.",
author = "Hana Koutnikova and Markku Laakso and Lu Lu and Roy Combe and Jussi Paananen and Teemu Kuulasmaa and Johanna Kuusisto and Hans-Ulrich H{\"a}ring and Torben Hansen and Oluf Pedersen and Ulf Smith and Markolf Hanefeld and Williams, {Robert W} and Johan Auwerx",
note = "Keywords: Adult; Aged; Animals; Blood Pressure; Cohort Studies; DNA-Binding Proteins; Female; Humans; Hypertension; Male; Mice; Mice, Inbred Strains; Middle Aged; Pedigree; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Transcription Factors",
year = "2009",
doi = "10.1371/journal.pgen.1000591",
language = "English",
volume = "5",
pages = "e1000591",
journal = "P L o S Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "8",

}

RIS

TY - JOUR

T1 - Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics

AU - Koutnikova, Hana

AU - Laakso, Markku

AU - Lu, Lu

AU - Combe, Roy

AU - Paananen, Jussi

AU - Kuulasmaa, Teemu

AU - Kuusisto, Johanna

AU - Häring, Hans-Ulrich

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Smith, Ulf

AU - Hanefeld, Markolf

AU - Williams, Robert W

AU - Auwerx, Johan

N1 - Keywords: Adult; Aged; Animals; Blood Pressure; Cohort Studies; DNA-Binding Proteins; Female; Humans; Hypertension; Male; Mice; Mice, Inbred Strains; Middle Aged; Pedigree; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Transcription Factors

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pgen.1000591

DO - 10.1371/journal.pgen.1000591

M3 - Journal article

C2 - 19662162

VL - 5

SP - e1000591

JO - P L o S Genetics

JF - P L o S Genetics

SN - 1553-7390

IS - 8

ER -

ID: 18765174