Article Text

PDF
AB0014 Gender-Dependent Association Between HLA-G 14B Insertion/Deletion Polymorphism and Rheumatoid Arthritis in Italian Patients
  1. M. Rubini1,
  2. E. Bonomo Roversi1,
  3. V. Aiello1,
  4. M.F. Khan1,
  5. P. Franceschelli1,
  6. R. Bassi Andreasi1,
  7. I. Farina2,
  8. E. Galuppi2,
  9. M. Govoni2
  1. 1Biomedical and Specialty Surgical Sciences
  2. 2Medical Sciences, University of Ferrara, Ferrara, Italy

Abstract

Background The human leukocyte antigen (HLA) region contributes to approximately half of the genetic susceptibility for Rheumatoid Arthritis (RA), and alleles at the HLA-DRB1 locus are associated with increased risk and more severe phenotype in RA, but this locus does not entirely explain HLA contribution to disease risk.

HLA-G is a non-classical low-polymorphic HLA molecule, characterized by limited tissue distribution under normal physiological conditions. It has been shown to play a major role in immunosuppression, inhibiting the activity of cytotoxic T-lymphocytes and natural killer cells. Such feature makes HLA-G an attractive candidate gene for susceptibility to immune-mediated diseases. A 14 bp insertion/deletion polymorphism in the 3'UTR region of gene (rs16375) seems to reduce the transcript stability and associates with lower HLA-G expression.

Objectives To investigate if the rs16375 variant influences the susceptibility to develop RA using a case/control model in Italian population.

Methods We genotyped rs16375 polymorphism in a cohort of 322 Italian RA patients and in a matched group of healthy control individuals. All subject were genotyped using TaqMan technology.

Results The frequency of ins/ins genotype was significantly higher among RA patients compared to controls, indicating that ins/ins homozygotes had an increased risk to develop RA (OR=1.7 95% CI 1.2-2.6). Stratifying subjects according to gender, it came out that rs16375 genotype-associated susceptibility to RA was restricted to female patients (OR=2.4 95% CI 1.3-4.2), while rs16375 genotype had no influence on RA risk among males.

Conclusions These results suggest that HLA-G could contribute to RA pathogenesis, and that the 14b insertion/deletion polymorphism could account for gender-associated differences in genetic susceptibility to develop RA.

Acknowledgements This study was party supported by FAR grant from University of Ferrara.

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.