title: Association of a complement receptor 1 gene variant with baseline erythrocyte sedimentation rate levels in patients starting anti-TNF therapy in a UK rheumatoid arthritis cohort: results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort.
abstract: Eligibility for anti-tumour necrosis factor (TNF) therapy in most European countries is restricted to severe, active rheumatoid arthritis (RA). The DAS28 score is a marker of disease severity and incorporates one of two inflammatory markers, erythrocyte sedimentation rate (ESR) or C-reactive protein. We aimed to determine the relation between genetic variants known to affect ESR and levels of ESR in patients with active RA. DNA samples were genotyped for four single-nucleotide polymorphisms (SNPs) rs7527798 (CR1L), rs6691117 (CR1), rs10903129 (TMEM57) and rs1043879 (C1orf63). The association between SNPs and baseline ESR, baseline DAS28-ESR, and change in DAS28-ESR was evaluated. Baseline ESR was significantly associated with CR1 rs6691117 genotype (P=0.01). No correlation was identified between baseline DAS28-ESR or change in DAS28-ESR. In conclusion, genetic variation in the gene encoding CR1 may alter ESR levels but not DAS28-ESR, indicating no adjustment for CR1 genotype is required in the assessment of patients with severe active RA.
authors.affiliation: Arthritis Research UK Epidemiology Unit, Manchester Academy of Health Science, University of Manchester, Manchester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Bluett
authors.affiliation: Arthritis Research UK Epidemiology Unit, Manchester Academy of Health Science, University of Manchester, Manchester, UK.
authors.forename: I
authors.initials: I
authors.lastname: Ibrahim
authors.affiliation: NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: D
authors.initials: D
authors.lastname: Plant
authors.affiliation: Arthritis Research UK Epidemiology Unit, Manchester Academy of Health Science, University of Manchester, Manchester, UK.
authors.forename: K L
authors.initials: KL
authors.lastname: Hyrich
authors.affiliation: 1] NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, The Leeds Teaching Hospitals NHS Trust, Leeds, UK [2] Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds, UK.
authors.forename: A W
authors.initials: AW
authors.lastname: Morgan
authors.affiliation: Department of Infection and Immunity, University of Sheffield Medical School, Sheffield, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Wilson
authors.affiliation: Musculoskeletal Research Group, Newcastle upon Tyne NHS Foundation Trust, Institute of Cellular Medicine, Newcastle University and NIHR Newcastle Biomedical Research Centre, Newcastle-upon-Tyne, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Isaacs
authors.affiliation: 1] Arthritis Research UK Epidemiology Unit, Manchester Academy of Health Science, University of Manchester, Manchester, UK [2] NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Barton
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000235:genetics; D005060:Europe; D005260:Female; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017463:Receptors, Complement 3b / Q000235:genetics*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: C509991:CR1 protein, human; D017463:Receptors, Complement 3b; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein