Dataset Information

Lectin, galactoside-binding, soluble, 3 rs4652 A/C gene variation and the risk for rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is a complex genetic disease. The lectin, galactoside-binding, soluble, 3 (LGALS3) gene, encodes a member of the galectin family of carbohydrate binding proteins, and is one of the best examples of a non-human leukocyte antigen gene associated with a risk for RA in various populations. In the current study, the association between LGALS3 rs4652 gene polymorphism and RA was examined. This case-control study was performed on the 120 patients with RA and 120 healthy subjects. Genomic DNA was extracted from whole blood, and gene polymorphism was tested using a tetra-primer amplification refractory mutation system-polymerase chain reaction. The results demonstrated that LGALS3 rs4652 AC genotype increased the risk of RA (OR=11.622, 95% CI=4.473-28.656; P=0.001) when compared with the AA genotype. However, the CC genotype and the C allele were not associated with RA. These findings indicated an association between LGALS3 rs4652 variation and the risk of RA in a sample of Iranian individuals. Further studies with larger sample sizes and populations of different ethnicities are required to validate our findings.

SUBMITTER: Atabaki M

PROVIDER: S-EPMC5351383 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Lectin, galactoside-binding, soluble, 3 rs4652 A/C gene variation and the risk for rheumatoid arthritis.

Atabaki Mahdi M Hashemi Mohammad M Daneshvar Hamid H Alijani Ebrahim E

Biomedical reports 20170109 2

Rheumatoid arthritis (RA) is a complex genetic disease. The lectin, galactoside-binding, soluble, 3 (LGALS3) gene, encodes a member of the galectin family of carbohydrate binding proteins, and is one of the best examples of a non-human leukocyte antigen gene associated with a risk for RA in various populations. In the current study, the association between LGALS3 rs4652 gene polymorphism and RA was examined. This case-control study was performed on the 120 patients with RA and 120 healthy subjec ...[more]

PMID: 28357081

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Project description:INTRODUCTION: Rheumatoid arthritis (RA) improves during pregnancy and flares after delivery. It has been hypothesized that high levels of the complement factor mannose-binding lectin (MBL) are associated with a favourable disease course of RA by facilitating the clearance of pathogenic immunoglobulin G (IgG) lacking galactose sugar moieties. During pregnancy, increased galactosylation of IgG and simultaneously increased MBL levels can be observed, with the latter being strictly related to maternal MBL genotypes. Therefore, increased MBL levels in concert with increased IgG galactosylation may be associated with pregnancy-induced improvement of RA. The objective of this study was to investigate whether MBL genotypes are associated with changes in RA disease activity and with changes in IgG galactosylation during pregnancy and in the postpartum period. We also studied the association between MBL genotypes and pregnancy outcomes in RA. METHODS: Serum from 216 patients with RA and 31 healthy controls participating in the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) Study was collected before, during and after pregnancy. IgG galactosylation was determined by performing matrix-assisted laser desorption/ionization time of flight mass spectrometry. Disease activity was determined using the internationally recognized Disease Activity Score 28 (DAS28). MBL genotypes were determined. The pregnancy outcome measures studied were gestational age, birth weight, miscarriage and hypertensive disorders. RESULTS: No association was found between the MBL genotype groups and changes in RA disease activity (P = 0.89) or changes in IgG galactosylation (patients, P = 0.75, and controls, P = 0.54) during pregnancy and in the postpartum period. Furthermore, MBL genotype groups were not related to the studied pregnancy outcome measures. CONCLUSIONS: This study does not provide evidence for a role for MBL in the improvement of RA during pregnancy or for a role for MBL in pregnancy outcome.

Project description:BackgroundRheumatoid arthritis (RA) is a systemic autoimmune disease associated with immune dysregulation and increased risk of infections. The presence of autoantibodies and immunoglobulin abnormalities indicates B-cell and antibody-secreting cell (ASC) dysfunction. We hypothesize that soluble factors associated with B-cell and ASC activity are decreased in RA patients and that this is linked to higher susceptibility to infections.MethodsUsing the Johns Hopkins Arthritis Cohort and Biorepository, we contrasted serum protein levels of soluble factors involved in B-cell activation (CD40, CD40L) and B-cell/ASC homing (CXCL10, CXCL11, and CXCL13) or survival (BAFF, APRIL, TACI, and BCMA) in 10 healthy subjects and 23 adult RA patients (aged 24-65 years). We subdivided RA patients into those with (n = 17) and those without infections (n = 6) within a 2-year period. In order to reduce the effect of RA treatment, we only included patients receiving methotrexate monotherapy or no RA treatments at baseline. Soluble serum protein levels of B-cell/ASC factors were quantified by multiplex immunoassays.ResultsWe identified that (1) serum levels of soluble BCMA, APRIL, CD40, and CD40L were significantly decreased in RA patients relative to healthy individuals; (2) serum soluble BCMA, predominantly released by ASC, correlated with serum concentrations of class-switched immunoglobulins, IgG and IgA; and (3) RA patients with a history of infections had significantly lower soluble BCMA levels compared with healthy donors and with RA patients without infections.ConclusionsOur study using soluble factors linked to B-cell/ASC activation and survival suggests that there is a paucity of ASC in a subset of RA patients and that this may be linked to altered antibody production and increased risk of infections. Further delineating the link between ASC and infection susceptibility in RA may optimize disease management and provide novel insights into disease pathogenesis that are susceptible to intervention.

Dataset Information

Lectin, galactoside-binding, soluble, 3 rs4652 A/C gene variation and the risk for rheumatoid arthritis.

Publications

Lectin, galactoside-binding, soluble, 3 rs4652 A/C gene variation and the risk for rheumatoid arthritis.

Similar Datasets

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