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A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure

Tutkimustuotosvertaisarvioitu

Standard

A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure. / Turpeinen, Hannu; Seppälä, Ilkka; Lyytikäinen, Leo Pekka; Raitoharju, Emma; Hutri-Kähönen, Nina; Levula, Mari; Oksala, Niku; Waldenberger, Melanie; Klopp, Norman; Illig, Thomas; Mononen, Nina; Laaksonen, Reijo; Raitakari, Olli; Kähönen, Mika; Lehtimäki, Terho; Pesu, Marko.

julkaisussa: HUMAN GENETICS, Vuosikerta 134, Nro 6, 01.06.2015, s. 627-636.

Tutkimustuotosvertaisarvioitu

Harvard

Turpeinen, H, Seppälä, I, Lyytikäinen, LP, Raitoharju, E, Hutri-Kähönen, N, Levula, M, Oksala, N, Waldenberger, M, Klopp, N, Illig, T, Mononen, N, Laaksonen, R, Raitakari, O, Kähönen, M, Lehtimäki, T & Pesu, M 2015, 'A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure', HUMAN GENETICS, Vuosikerta. 134, Nro 6, Sivut 627-636. https://doi.org/10.1007/s00439-015-1546-5

APA

Turpeinen, H., Seppälä, I., Lyytikäinen, L. P., Raitoharju, E., Hutri-Kähönen, N., Levula, M., ... Pesu, M. (2015). A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure. HUMAN GENETICS, 134(6), 627-636. https://doi.org/10.1007/s00439-015-1546-5

Vancouver

Author

Turpeinen, Hannu ; Seppälä, Ilkka ; Lyytikäinen, Leo Pekka ; Raitoharju, Emma ; Hutri-Kähönen, Nina ; Levula, Mari ; Oksala, Niku ; Waldenberger, Melanie ; Klopp, Norman ; Illig, Thomas ; Mononen, Nina ; Laaksonen, Reijo ; Raitakari, Olli ; Kähönen, Mika ; Lehtimäki, Terho ; Pesu, Marko. / A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure. Julkaisussa: HUMAN GENETICS. 2015 ; Vuosikerta 134, Nro 6. Sivut 627-636.

Bibtex - Lataa

@article{50adb88d6fef46fca68a5fe5234d86a2,
title = "A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure",
abstract = "Proprotein convertase subtilisin/kexin (PCSK) enzymes cleave and convert their immature substrates into biologically active forms. Polymorphisms in the PCSK genes have been reported to associate with human diseases and phenotypes, including hypercholesterolemia and blood pressure (BP), and targeting PCSKs is considered a promising future form of drug therapy. PCSK processing is readily induced upon upregulation of the enzyme, but the genetic factors contributing to PCSK expression have not been thoroughly characterized. To gain a comprehensive understanding of the genetic regulation of PCSK expression, we performed, for the first time, a genome-wide expression quantitative trait loci (eQTL) analysis using mRNA expression in >1400 human peripheral blood samples from the Cardiovascular Risk in Young Finns Study and ca. ten million single-nucleotide polymorphisms (SNPs). The expression data showed clear expression for FURIN, PCSK5, PCSK7 and MBTPS1 (membrane-bound transcription factor peptidase, site 1) mRNAs in virtually all tested samples. A discovery analysis demonstrated a genome-wide significant (p −8) association with the selected PCSK probes for 1024 variants, which were located at ten independent loci. Of these loci, 5/10 could be confirmed to regulate PCSK expression in two additional and independent sample sets. Finally, a phenotypic analysis demonstrated that a novel cis-eQTL SNP rs4702 for FURIN is strongly associated with both diastolic (p = 0.012) and systolic (p = 0.035) BP levels, as well as peripheral vascular resistance (p = 0.003). These findings indicate that the expression of the PCSK enzymes is regulated by genetic factors, which have biological roles in health and disease.",
author = "Hannu Turpeinen and Ilkka Sepp{\"a}l{\"a} and Lyytik{\"a}inen, {Leo Pekka} and Emma Raitoharju and Nina Hutri-K{\"a}h{\"o}nen and Mari Levula and Niku Oksala and Melanie Waldenberger and Norman Klopp and Thomas Illig and Nina Mononen and Reijo Laaksonen and Olli Raitakari and Mika K{\"a}h{\"o}nen and Terho Lehtim{\"a}ki and Marko Pesu",
year = "2015",
month = "6",
day = "1",
doi = "10.1007/s00439-015-1546-5",
language = "English",
volume = "134",
pages = "627--636",
journal = "HUMAN GENETICS",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "6",

}

RIS (suitable for import to EndNote) - Lataa

TY - JOUR

T1 - A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure

AU - Turpeinen, Hannu

AU - Seppälä, Ilkka

AU - Lyytikäinen, Leo Pekka

AU - Raitoharju, Emma

AU - Hutri-Kähönen, Nina

AU - Levula, Mari

AU - Oksala, Niku

AU - Waldenberger, Melanie

AU - Klopp, Norman

AU - Illig, Thomas

AU - Mononen, Nina

AU - Laaksonen, Reijo

AU - Raitakari, Olli

AU - Kähönen, Mika

AU - Lehtimäki, Terho

AU - Pesu, Marko

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Proprotein convertase subtilisin/kexin (PCSK) enzymes cleave and convert their immature substrates into biologically active forms. Polymorphisms in the PCSK genes have been reported to associate with human diseases and phenotypes, including hypercholesterolemia and blood pressure (BP), and targeting PCSKs is considered a promising future form of drug therapy. PCSK processing is readily induced upon upregulation of the enzyme, but the genetic factors contributing to PCSK expression have not been thoroughly characterized. To gain a comprehensive understanding of the genetic regulation of PCSK expression, we performed, for the first time, a genome-wide expression quantitative trait loci (eQTL) analysis using mRNA expression in >1400 human peripheral blood samples from the Cardiovascular Risk in Young Finns Study and ca. ten million single-nucleotide polymorphisms (SNPs). The expression data showed clear expression for FURIN, PCSK5, PCSK7 and MBTPS1 (membrane-bound transcription factor peptidase, site 1) mRNAs in virtually all tested samples. A discovery analysis demonstrated a genome-wide significant (p −8) association with the selected PCSK probes for 1024 variants, which were located at ten independent loci. Of these loci, 5/10 could be confirmed to regulate PCSK expression in two additional and independent sample sets. Finally, a phenotypic analysis demonstrated that a novel cis-eQTL SNP rs4702 for FURIN is strongly associated with both diastolic (p = 0.012) and systolic (p = 0.035) BP levels, as well as peripheral vascular resistance (p = 0.003). These findings indicate that the expression of the PCSK enzymes is regulated by genetic factors, which have biological roles in health and disease.

AB - Proprotein convertase subtilisin/kexin (PCSK) enzymes cleave and convert their immature substrates into biologically active forms. Polymorphisms in the PCSK genes have been reported to associate with human diseases and phenotypes, including hypercholesterolemia and blood pressure (BP), and targeting PCSKs is considered a promising future form of drug therapy. PCSK processing is readily induced upon upregulation of the enzyme, but the genetic factors contributing to PCSK expression have not been thoroughly characterized. To gain a comprehensive understanding of the genetic regulation of PCSK expression, we performed, for the first time, a genome-wide expression quantitative trait loci (eQTL) analysis using mRNA expression in >1400 human peripheral blood samples from the Cardiovascular Risk in Young Finns Study and ca. ten million single-nucleotide polymorphisms (SNPs). The expression data showed clear expression for FURIN, PCSK5, PCSK7 and MBTPS1 (membrane-bound transcription factor peptidase, site 1) mRNAs in virtually all tested samples. A discovery analysis demonstrated a genome-wide significant (p −8) association with the selected PCSK probes for 1024 variants, which were located at ten independent loci. Of these loci, 5/10 could be confirmed to regulate PCSK expression in two additional and independent sample sets. Finally, a phenotypic analysis demonstrated that a novel cis-eQTL SNP rs4702 for FURIN is strongly associated with both diastolic (p = 0.012) and systolic (p = 0.035) BP levels, as well as peripheral vascular resistance (p = 0.003). These findings indicate that the expression of the PCSK enzymes is regulated by genetic factors, which have biological roles in health and disease.

UR - http://www.scopus.com/inward/record.url?scp=84936752765&partnerID=8YFLogxK

U2 - 10.1007/s00439-015-1546-5

DO - 10.1007/s00439-015-1546-5

M3 - Article

VL - 134

SP - 627

EP - 636

JO - HUMAN GENETICS

JF - HUMAN GENETICS

SN - 0340-6717

IS - 6

ER -