Functional characterisation of ADIPOQ variants using individuals recruited by genotype.

Autor: Lee BP; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, Devon, EX2 5DW, UK., Lloyd-Laney HO; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, Devon, EX2 5DW, UK., Locke JM; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, Devon, EX2 5DW, UK., McCulloch LJ; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, Devon, EX2 5DW, UK., Knight B; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, Devon, EX2 5DW, UK., Yaghootkar H; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, Devon, EX2 5DW, UK., Cory G; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, Devon, EX2 5DW, UK., Kos K; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, Devon, EX2 5DW, UK., Frayling TM; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, Devon, EX2 5DW, UK., Harries LW; Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, Devon, EX2 5DW, UK. Electronic address: L.W.Harries@exeter.ac.uk.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2016 Jun 15; Vol. 428, pp. 49-57. Date of Electronic Publication: 2016 Mar 17.
DOI: 10.1016/j.mce.2016.03.020
Abstrakt: Four non-coding GWAS variants in or near the ADIPOQ gene (rs17300539, rs17366653, rs3821799 and rs56354395) together explain 4% of the variation in circulating adiponectin. The functional basis for this is unknown. We tested the effect of these variants on ADIPOQ transcription, splicing and stability respectively in adipose tissue samples from participants recruited by rs17366653 genotype. Transcripts carrying rs17300539 demonstrated a 17% increase in expression (p = 0.001). Variant rs17366653 was associated with disruption of ADIPOQ splicing leading to a 7 fold increase in levels of a non-functional transcript (p = 0.002). Transcripts carrying rs56354395 demonstrated a 59% decrease in expression (p = <0.0001). No effects of rs3821799 genotype on expression was observed. Association between variation in the ADIPOQ gene and serum adiponectin may arise from effects on mRNA transcription, splicing or stability. These studies illustrate the utility of recruit-by-genotype studies in relevant human tissues in functional interpretation of GWAS signals.
(Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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