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.
abstract: BACKGROUND
  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-iT(TM) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, Tampere, Finland. juulia.jylhava@uta.fi
authors.forename: Juulia
authors.initials: J
authors.lastname: Jylhävä
authors.forename: Leo-Pekka
authors.initials: LP
authors.lastname: Lyytikäinen
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Nina
authors.initials: N
authors.lastname: Hutri-Kähönen
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.forename: Jorma
authors.initials: J
authors.lastname: Viikari
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004247:DNA / Q000097:blood; D005260:Female; D005387:Finland; D056726:Genetic Association Studies; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D000099148:UGT1A1 Enzyme
chemical_list: D004247:DNA; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme