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AB0010 Hla-g 14-bp insertion/deletion polymorphism modulates MTX therapeutic effect in a cohort of patients with rheumatoid arthritis
  1. C. Brenol1,
  2. T.D. Veit2,
  3. P. Martineli3,
  4. J.C. Brenol1,
  5. C. Silva3,
  6. C. Hinckel3,
  7. J.A. Chies2,
  8. R. Xavier1
  9. and Rheumatoid Arthritis Research Group of Hospital de Clínicas de Porto Alegre
  1. 1Internal Medicine
  2. 2Genetics
  3. 3Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil

Abstract

Background In recent years, a convincing body of scientific evidence has indicated that the expression of human leukocyte antigen-G (HLA-G), a non-classical major histocompatibility complex (MHC) class I molecule, plays a role in regulation of inflammation in autoimmune diseases [1]. Polymorphisms in this gene, therefore, are reasonable candidates for susceptibility and pharmacogenetics studies in RA.

Objectives We sought to determine whether the 14-bp insertion/deletion polymorphism in exon 8 of the HLA-G gene is associated with susceptibility to RA, clinical features, or response to MTX therapy.

Methods We determined the HLA-G 14-bp insertion/deletion polymorphism genotypes in a prospective cohort of 309 consecutive RA patients and 294 healthy controls, and looked for associations between genotype and clinical features of RA. Multivariate analyses were performed to investigate the effect of homozygosity for the -14/-14 bp genotype on changes in DAS28 in response to MTX therapy in a subgroup of 188 RA patients.

Results Among the 309 RA patients, no correlations were observed between allele or genotype frequencies of the HLA-G gene polymorphism and clinical features, including disease activity scores and functional scores. No significant differences were observed in the genotype and allele frequencies between RA patients and controls. In the subgroup evaluated for clinical response to MTX, we observed a decrease in mean DAS28 over the course of the study. Furthermore, a better response to MTX treatment, measured by adjusted mean of DAS28 change, was observed in those patients with the HLA-G -14/-14-bp genotype, which was not observed among other genotypes (table 1).

Table 1.

Multivariate analyses for disease activity scores changes

Conclusions Homozygosity for the 14 bp deletion polymorphism within exon 8 of the HLA-G gene was associated with a better response to MTX in a prospective cohort of patients with RA. This is a plausible genetic marker for predicting response to MTX therapy in RA.

  1. Baricordi, O.R., et al., HLA-G and inflammatory diseases. Inflamm Allergy Drug Targets. 2008, 7(2): p. 67-74.

Disclosure of Interest None Declared

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