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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: 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-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. 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 concentrations.

SUBMITTER: Jylhava J

PROVIDER: S-EPMC3325226 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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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.

Jylhävä Juulia J Lyytikäinen Leo-Pekka LP Kähönen Mika M Hutri-Kähönen Nina N Kettunen Johannes J Viikari Jorma J Raitakari Olli T OT Lehtimäki Terho T Hurme Mikko M

PloS one 20120412 4

<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 cont ...[more]

PMID: 22511988

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Project description:ObjectiveSedentary behaviour may contribute to the development of obesity. We investigated the relations between different types of sedentary behaviour and adiposity markers in a well-characterised adult population after controlling for a wide range of potential confounders.DesignCross-sectional study.SettingThe Cardiovascular Risk in Young Finns Multicenter Study. Participants Sedentary time (TV viewing, computer time, reading, music/radio listening and other relaxation) was assessed with a questionnaire for 1084 women and 909 men aged 30-45 years. Other study variables included occupational and leisure-time physical activity, sleep duration, socioeconomic status, smoking, alcohol consumption, energy intake, adherence to the recommended diet, multiple individual food items, age and genetic variants associated with body mass index (BMI). Primary outcome measures BMI in kg/m(2) and waist circumference (WC in cm).ResultsOf the different sedentary behaviour types, TV viewing was most consistently related to higher BMI and WC, both in men and women. One additional daily TV hour was associated with a 1.81±0.44 cm larger WC in women and 2 cm±0.44 cm in men (both p<0.0001). The association with TV was diluted, but remained highly significant after adjustments with all measured covariates, including several potentially obesogenic food items associated with TV viewing. The intakes of food items such as sausage, beer and soft drinks were directly associated with TV viewing, while the intakes of oat and barley, fish, and fruits and berries were associated indirectly. After these adjustments, non-TV sedentary behaviour remained associated with adiposity indices only in women.ConclusionsOut of the different types of sedentary behaviour, TV viewing was most consistently associated with adiposity markers in adults. Partial dilution of these associations after adjustments for covariates suggests that the obesogenic effects of TV viewing are partly mediated by other lifestyle factors.

Dataset Information

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.

Publications

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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