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

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dc.contributor.author Jylhävä, Juulia -
dc.contributor.author Lyytikäinen, Leo-Pekka -
dc.contributor.author Kähönen, Mika -
dc.contributor.author Hutri-Kähönen, Nina -
dc.contributor.author Kettunen, Johannes -
dc.contributor.author Viikari, Jorma -
dc.contributor.author Raitakari, Olli T -
dc.contributor.author Lehtimäki, Terho -
dc.contributor.author Hurme, Mikko -
dc.date.accessioned 2012-06-17T20:15:40Z
dc.date.available 2012-06-16 08:47:45 -
dc.date.available 2012-06-17T20:15:40Z
dc.date.issued 2012 -
dc.identifier.issn 1932-6203 -
dc.identifier.uri http://tampub.uta.fi/handle/10024/66112
dc.description Public Library of science open access -
dc.description.abstract Introduction 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. Methods 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-iTTM high sensitivity DNA assay was used to measure cf-DNA directly from serum. Results 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. Conclusion 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 -
dc.language.iso en -
dc.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 -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal article| -
dc.identifier.urn urn:nbn:uta-3-982 -
dc.identifier.doi 10.1371/journal.pone.0035426 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Biolääketieteet | en=Biomedicine| -
dc.administrativeunit fi=Lääketieteen yksikkö | en=School of Medicine| -
dc.journal.title Plos One -
dc.journal.volume 7 -
dc.journal.number 4 -
dc.journal.volumepagerange 1-7 -
dc.oldstats 23 -

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