Mannan Binding Lectin (MBL) genotypes coding for high MBL serum levels are associated with rheumatoid factor negative rheumatoid arthritis in never smokers.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
CitationArthritis Res. Ther. 2011, 13(2):R65
AbstractINTRODUCTION: Previous studies have provided inconsistent results on whether variants in the MBL2 gene, coding for the complement-activating mannan-binding lectin (MBL) protein, associate with rheumatoid arthritis (RA). We re-evaluated this in context of the main environmental and genetic risk factors (smoking, HLA-DRB1 'shared epitope' (SE), PTPN22*620W), which predispose to rheumatoid factor (RF) and/or anti-citrullinated-protein antibody (ACPA)-positive RA. METHODS: In this population-based EIRA study, rheumatoid factor (RF), ACPA, smoking, SE and PTPN22*620W status was determined in incident RA cases and matched controls. MBL-high (n = 1330) and MBL-low (n = 1257) genotypes predicting MBL levels were constructed from four promoter and exon-1 polymorphisms in the MBL2 gene. Odds ratios with 95% confidence interval (OR, 95% CI) were calculated by logistic regression. In extended families (n = 316), previously reported data were re-analyzed, considering RF and smoking. RESULTS: MBL-high genotypes tended to be associated with RF-negative (OR = 1.20, 95% CI 0.96-1.51) but not RF-positive (OR = 1.00, 95% CI 0.83-1.20) RA. Results divided by ACPA status did not differ. When stratified for smoking, MBL-high genotype was strongly associated with RF-negative RA in never smokers (OR = 1.82, 95% CI 1.24-2.69) but not in ever smokers (OR = 0.96, 95% CI 0.73-1.30). In never smokers, the association was observed in both the RF-negative/ACPA-negative (OR = 1.67, 95% CI 1.10-2.55) and RF-negative/ACPA-positive subgroups (OR = 3.07, 95% CI 1.37-6.89), and remained on an SE/PTPN22*620W negative background. In the extended families, the reported association between high MBL and RA was in fact confined to never smokers. CONCLUSIONS: High MBL may predispose to RF-negative RA but only in individuals who have never smoked. This illustrates the importance of phenotypic subgrouping in genetic studies.
DescriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.
RightsArchived with thanks to Arthritis research & therapy
- Smoking interacts with HLA-DRB1 shared epitope in the development of anti-citrullinated protein antibody-positive rheumatoid arthritis: results from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA).
- Authors: Too CL, Yahya A, Murad S, Dhaliwal JS, Larsson PT, Muhamad NA, Abdullah NA, Mustafa AN, Klareskog L, Alfredsson L, Padyukov L, Bengtsson C, MyEIRA study group.
- Issue date: 2012 Apr 26
- A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis.
- Authors: Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L
- Issue date: 2004 Oct
- Smoking and polymorphisms of genes encoding mannose-binding lectin and surfactant protein-D in patients with rheumatoid arthritis.
- Authors: Kristiansen M, Frisch M, Madsen HO, Garred P, Jacobsen S
- Issue date: 2014 Mar
- Smoking increases rheumatoid arthritis susceptibility in individuals carrying the HLA-DRB1 shared epitope, regardless of rheumatoid factor or anti-cyclic citrullinated peptide antibody status.
- Authors: Bang SY, Lee KH, Cho SK, Lee HS, Lee KW, Bae SC
- Issue date: 2010 Feb
- Relationship among the HLA-DRB1 shared epitope, smoking, and rheumatoid factor production in rheumatoid arthritis.
- Authors: Mattey DL, Dawes PT, Clarke S, Fisher J, Brownfield A, Thomson W, Hajeer AH, Ollier WE
- Issue date: 2002 Aug