Mannan Binding Lectin MBL genotypes coding for high MBL serum levels are associated with rheumatoid factor negative rheumatoid arthritis in never smokersReportar como inadecuado




Mannan Binding Lectin MBL genotypes coding for high MBL serum levels are associated with rheumatoid factor negative rheumatoid arthritis in never smokers - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Arthritis Research and Therapy

, 13:R65

First Online: 15 April 2011Received: 25 November 2010Revised: 24 February 2011Accepted: 15 April 2011

Abstract

IntroductionPrevious 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.

MethodsIn 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.

ResultsMBL-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.

ConclusionsHigh 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.

AbbreviationsACPAanti-citrullinated peptide antibody

CIconfidence interval

EIRAEpidemiological Investigation of Rheumatoid Arthritis

ELISAenzyme-linked immunosorbent assay

HLAhuman leucocyte antigen

Igimmunoglobulin

MBLmannan-binding lectin

ORodds ratio

PCRpolymerase chain reaction

RArheumatoid arthritis

RFrheumatoid factor

SEshared epitope

SNOS-nitrosylation.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3321 contains supplementary material, which is available to authorized users.

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Autor: Saedis Saevarsdottir - Bo Ding - Kristjan Steinsson - Gerdur Grondal - Helgi Valdimarsson - Lars Alfredsson - Lars Klaresko

Fuente: https://link.springer.com/







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