A genome-wide association study identifies UGT1A1 as a regulator of serum cell-free DNA in young adults: The Cardiovascular Risk in Young Finns Study.

<h4>Introduction</h4>Circulating cell-free DNA (cf-DNA) is a useful indicator of cell death, and it can also be used to predict outcomes in various clinical disorders. Several innate immune mechanisms are known to be involved in eliminating DNA and chromatin-related material as part of t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Juulia Jylhävä, Leo-Pekka Lyytikäinen, Mika Kähönen, Nina Hutri-Kähönen, Johannes Kettunen, Jorma Viikari, Olli T Raitakari, Terho Lehtimäki, Mikko Hurme
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ba9d5a5af5dd443b8e8ef0cdec5a09d9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ba9d5a5af5dd443b8e8ef0cdec5a09d9
record_format	dspace
spelling	oai:doaj.org-article:ba9d5a5af5dd443b8e8ef0cdec5a09d92021-11-18T07:22:23ZA genome-wide association study identifies UGT1A1 as a regulator of serum cell-free DNA in young adults: The Cardiovascular Risk in Young Finns Study.1932-620310.1371/journal.pone.0035426https://doaj.org/article/ba9d5a5af5dd443b8e8ef0cdec5a09d92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22511988/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>Circulating cell-free DNA (cf-DNA) is a useful indicator of cell death, and it can also be used to predict outcomes in various clinical disorders. Several innate immune mechanisms are known to be involved in eliminating DNA and chromatin-related material as part of the inhibition of potentially harmful autoimmune responses. However, the exact molecular mechanism underlying the clearance of circulating cf-DNA is currently unclear.<h4>Methods</h4>To examine the mechanisms controlling serum levels of cf-DNA, we carried out a genome-wide association analysis (GWA) in a cohort of young adults (aged 24-39 years; n = 1841; 1018 women and 823 men) participating in the Cardiovascular Risk in Young Finns Study. Genotyping was performed with a custom-built Illumina Human 670 k BeadChip. The Quant-iT(TM) high sensitivity DNA assay was used to measure cf-DNA directly from serum.<h4>Results</h4>The results revealed that 110 single nucleotide polymorphisms (SNPs) were associated with serum cf-DNA with genome-wide significance (p<5×10(-8)). All of these significant SNPs were localised to chromosome 2q37, near the UDP-glucuronosyltransferase 1 (UGT1) family locus, and the most significant SNPs localised within the UGT1 polypeptide A1 (UGT1A1) gene region.<h4>Conclusion</h4>The UGT1A1 enzyme catalyses the detoxification of several drugs and the turnover of many xenobiotic and endogenous compounds by glucuronidating its substrates. These data indicate that UGT1A1-associated processes are also involved in the regulation of serum cf-DNA concentrations.Juulia JylhäväLeo-Pekka LyytikäinenMika KähönenNina Hutri-KähönenJohannes KettunenJorma ViikariOlli T RaitakariTerho LehtimäkiMikko HurmePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35426 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Juulia Jylhävä Leo-Pekka Lyytikäinen Mika Kähönen Nina Hutri-Kähönen Johannes Kettunen Jorma Viikari Olli T Raitakari Terho Lehtimäki Mikko Hurme A genome-wide association study identifies UGT1A1 as a regulator of serum cell-free DNA in young adults: The Cardiovascular Risk in Young Finns Study.
description	<h4>Introduction</h4>Circulating cell-free DNA (cf-DNA) is a useful indicator of cell death, and it can also be used to predict outcomes in various clinical disorders. Several innate immune mechanisms are known to be involved in eliminating DNA and chromatin-related material as part of the inhibition of potentially harmful autoimmune responses. However, the exact molecular mechanism underlying the clearance of circulating cf-DNA is currently unclear.<h4>Methods</h4>To examine the mechanisms controlling serum levels of cf-DNA, we carried out a genome-wide association analysis (GWA) in a cohort of young adults (aged 24-39 years; n = 1841; 1018 women and 823 men) participating in the Cardiovascular Risk in Young Finns Study. Genotyping was performed with a custom-built Illumina Human 670 k BeadChip. The Quant-iT(TM) high sensitivity DNA assay was used to measure cf-DNA directly from serum.<h4>Results</h4>The results revealed that 110 single nucleotide polymorphisms (SNPs) were associated with serum cf-DNA with genome-wide significance (p<5×10(-8)). All of these significant SNPs were localised to chromosome 2q37, near the UDP-glucuronosyltransferase 1 (UGT1) family locus, and the most significant SNPs localised within the UGT1 polypeptide A1 (UGT1A1) gene region.<h4>Conclusion</h4>The UGT1A1 enzyme catalyses the detoxification of several drugs and the turnover of many xenobiotic and endogenous compounds by glucuronidating its substrates. These data indicate that UGT1A1-associated processes are also involved in the regulation of serum cf-DNA concentrations.
format	article
author	Juulia Jylhävä Leo-Pekka Lyytikäinen Mika Kähönen Nina Hutri-Kähönen Johannes Kettunen Jorma Viikari Olli T Raitakari Terho Lehtimäki Mikko Hurme
author_facet	Juulia Jylhävä Leo-Pekka Lyytikäinen Mika Kähönen Nina Hutri-Kähönen Johannes Kettunen Jorma Viikari Olli T Raitakari Terho Lehtimäki Mikko Hurme
author_sort	Juulia Jylhävä
title	A genome-wide association study identifies UGT1A1 as a regulator of serum cell-free DNA in young adults: The Cardiovascular Risk in Young Finns Study.
title_short	A genome-wide association study identifies UGT1A1 as a regulator of serum cell-free DNA in young adults: The Cardiovascular Risk in Young Finns Study.
title_full	A genome-wide association study identifies UGT1A1 as a regulator of serum cell-free DNA in young adults: The Cardiovascular Risk in Young Finns Study.
title_fullStr	A genome-wide association study identifies UGT1A1 as a regulator of serum cell-free DNA in young adults: The Cardiovascular Risk in Young Finns Study.
title_full_unstemmed	A genome-wide association study identifies UGT1A1 as a regulator of serum cell-free DNA in young adults: The Cardiovascular Risk in Young Finns Study.
title_sort	genome-wide association study identifies ugt1a1 as a regulator of serum cell-free dna in young adults: the cardiovascular risk in young finns study.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/ba9d5a5af5dd443b8e8ef0cdec5a09d9
work_keys_str_mv	AT juuliajylhava agenomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT leopekkalyytikainen agenomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT mikakahonen agenomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT ninahutrikahonen agenomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT johanneskettunen agenomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT jormaviikari agenomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT ollitraitakari agenomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT terholehtimaki agenomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT mikkohurme agenomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT juuliajylhava genomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT leopekkalyytikainen genomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT mikakahonen genomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT ninahutrikahonen genomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT johanneskettunen genomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT jormaviikari genomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT ollitraitakari genomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT terholehtimaki genomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy AT mikkohurme genomewideassociationstudyidentifiesugt1a1asaregulatorofserumcellfreednainyoungadultsthecardiovascularriskinyoungfinnsstudy
_version_	1718423559650410496

A genome-wide association study identifies UGT1A1 as a regulator of serum cell-free DNA in young adults: The Cardiovascular Risk in Young Finns Study.

Ejemplares similares