Personal, non-commercial use only. The Journal of Rheumatology. Copyright © 2004. All rights reserved. The Journal of Rheumatology 2004; 31:3 442 From the Arthritis and Rheumatism Campaign Epidemiology Unit and the Centre for Integrated Genominc Medical Research, University of Manchester, Manchester, UK. Supported by the UK Arthritis Research Campaign. A. Barton, MRCP, Clinical Lecturer; H. Platt, BSc, Experimental Officer; F. Salway, MSc, Experimental Officer; D. Symmons, FRCP, Professor of Rheumatology and Musculoskeletal Epidemiology; M. Lunt, PhD, Research Fellow; J. Worthington, PhD, Reader in Genetic Epidemiology, A. Silman, FRCP, Professor of Rheumatic Disease Epidemiology. Address reprint requests to Dr. ABarton, ARC-EU, Stopford Building, University of Manchester, UK. E-mail: ABarton@fs1.ser.man.ac.uk Submitted March 24, 2003; revision accepted September 26, 2003. Twin studies suggest a substantial genetic contribution to rheumatoid arthritis (RA) susceptibility and family studies have shown that first-degree relatives of patients with RA are at increased risk 1 . However, the increased risk in probands recruited from a community based setting is modest compared with hospital-recruited patients 2 . As hospital-based patients are likely to have more severe disease, this suggests that genetic factors may play a greater role in determining disease severity and outcome. Mannose binding lectin (MBL) is involved in the innate immune system and it has been suggested that impairment of innate immunity as a result of MBL deficiency may lead to increased presentation of antigens to the host, a reduction in self-tolerance, and susceptibility to autoimmunity 3 . There are a number of single nucleotide polymorphisms (SNP) of the MBL gene (MBL) and haplotypes have been defined, some of which encode high and others low levels of MBL protein production. The wild type MBL allele is referred to as A. Structural polymorphisms exist at 3 positions: in codon 52*C/T, codon 54*G/A and codon 57*G/A, and the presence of such a variant allele at any of these sites is referred to as O. MBL protein levels are higher in individ- uals with an A/A than A/O genotype and MBL levels are virtually undetectable in individuals with O/O genotype. In addition, 2 promoter variants exist: the MBL-550*C/G (H/L) SNP, which has little effect on levels, and the MBL- 221*G/C (Y/X) SNP, which has a profound lowering effect when 2 copies are present. Studies have reported association of MBL polymor- phisms with susceptibility to RA but the results have been conflicting 4-11 . The variation in these reports may result from differences in the patient cohorts investigated, particu- larly if MBL polymorphisms are more important in deter- mining disease severity rather than susceptibility. Several studies have therefore attempted to address this issue and have reported association of MBL polymorphisms, including haplotypes known to encode low MBL protein production, with development of erosions in RA 6,7,9,10 . Furthermore, studies have also investigated MBL protein levels with outcome in RA 6,7,9,11,12 , including 2 prospective studies of RA patients in which low MBL protein levels were associated with development of erosions 9,12 . Polymorphisms in the Mannose Binding Lectin (MBL) Gene Are Not Associated with Radiographic Erosions in Rheumatoid or Inflammatory Polyarthritis ANNE BARTON, HAZEL PLATT, FIONA SALWAY, DEBORAH SYMMONS, MARK LUNT, JANE WORTHINGTON, and ALAN SILMAN ABSTRACT. Objective. To investigate the association between the mannose binding lectin gene (MBL) promoter and structural single nucleotide polymorphisms (SNP) with development of erosions in a primary care inception cohort of patients with inflammatory polyarthritis (IP). Methods. DNA was available from 438 patients with IP and radiographic data were available for all patients at 5 years. Four SNP [MBL-550*C/G (H/L), MBL-221*G/C (Y/X), MBL codon 52*C/T, and MBL codon 54*G/A] mapping to the MBL gene were genotyped using primer extension techniques. Allele frequencies were compared between IP cases with erosions by 5 years and those without. Results. None of the SNP were associated with erosive outcomes by 5 years. Furthermore there was no association with Larsen score by 1 or 5 years or with the change in Larsen score between 1 and 5 years. Similarly, the genotype combinations known to encode for low MBL protein production were not associated with erosive outcome in the IP cohort as a whole or in those with rheumatoid arthritis (RA) by 5 years. Conclusion. Polymorphism within the MBL gene is not associated with presence or extent of erosions by 5 years in patients with RA or IP. (J Rheumatol 2004;31:442–7) Key Indexing Terms: MBL RHEUMATOID ARTHRITIS GENETICS INFLAMMATORY ARTHRITIS EROSIONS Personal, non-commercial use only. The Journal of Rheumatology Copyright © 2004. All rights reserved. www.jrheum.org Downloaded on January 13, 2022 from