title: Previously reported PDE3A-SLCO1C1 genetic variant does not correlate with anti-TNF response in a large UK rheumatoid arthritis cohort.
abstract: A genetic variant has recently reached genome-wide significance for association with TNF-inhibitor response in rheumatoid arthritis patients. Here we undertake a replication study in a UK Caucasian population to test for association with TNF-inhibitor response.
  
  
  
  The genetic variant, rs3794271, located within the PDE3A-SLCO1C1 locus was analyzed for correlation with treatment response using both the EULAR classification criteria and absolute change in (Δ)DAS28 scores as outcome measures.
  
  
  
  Genotype data were available from 1750 TNF-inhibitor treated individuals. However, no evidence for association was observed (EULAR: p = 0.91 and ΔDAS28: p = 0.93). Furthermore, no significant associations were observed upon stratification by the anti-TNF received (p > 0.05).
  
  
  
  In the largest replication cohort conducted to date, no evidence for association was observed.
authors.affiliation: Arthritis Research UK, Centre for Genetics & Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK.
authors.forename: Samantha Louise
authors.initials: SL
authors.lastname: Smith
authors.affiliation: NIHR Manchester Musculoskeletal BRU, Central Manchester Foundation Trust & University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Darren
authors.initials: D
authors.lastname: Plant
authors.affiliation: Arthritis Research UK, Centre for Genetics & Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK.
authors.forename: Xiu Hue
authors.initials: XH
authors.lastname: Lee
authors.affiliation: Arthritis Research UK, Centre for Genetics & Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Massey
authors.affiliation: Arthritis Research UK, Centre for Epidemiology, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK.
authors.forename: Kimme
authors.initials: K
authors.lastname: Hyrich
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, UK.
authors.forename: Ann W
authors.initials: AW
authors.lastname: Morgan
authors.affiliation: UCD School of Medicine & Medical Science, Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Wilson
authors.affiliation: NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne NHS Foundation Trust & Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: John
authors.initials: J
authors.lastname: Isaacs
authors.affiliation: Arthritis Research UK, Centre for Genetics & Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK.|NIHR Manchester Musculoskeletal BRU, Central Manchester Foundation Trust & University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D006113:United Kingdom
chemical_list: D018501:Antirheumatic Agents; D027361:Organic Anion Transporters; C473187:SLCO1C1 protein, human; D014409:Tumor Necrosis Factor-alpha; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517287:PDE3A protein, human
keywords: TNF inhibitors; biomarker; rheumatoid arthritis; single nucleotide polymorphism; treatment response