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THU0479 Dheas-Associated Genotypes Contribute to Adrenal Androgen Hypofunction in RA
  1. L. Chovanova1,2,
  2. M. Mravcova2,
  3. R. Imrich1,2,
  4. J. Rovensky3,
  5. L. Paulikova2,
  6. M. Rakicka2,
  7. A. Marko2,
  8. A. Penesova2,
  9. H. Radner4,
  10. G. Steiner4,
  11. J. Smolen4,
  12. M. Vlcek1,2
  1. 1Center for Molecular Medicine SAS
  2. 2Institute of Experimental Endocrinology SAS, Bratislava
  3. 3National Institute of Rheumatic Diseases, Piestany, Slovakia
  4. 4Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria

Abstract

Background Lower levels of dehydroepiandrosterone sulphate (DHEAS) were found in chronic inflammatory diseases such as rheumatoid arthritis (RA), however, mechanisms for this decrease remains unclear. Recently, several genes has been found to be associated with lower DHEAS levels [1].

Objectives The aim of our study was to analyze frequency of selected single nucleotide polymorphisms (SNPs) known to be associated with low DHEAS in RA patients and their impact on DHEAS levels during disease.

Methods 1034 participants (438 RA, 596 controls) were analyzed for SNPs in genes ZKSCAN5 (rs11761528), SULT2A1 (rs2637125), HHEX (rs2497306) and ARPC1A (rs740160) by real-time PCR genotyping assay. Serum DHEAS concentration was measured in 156 RA patients and 102 healthy controls by ELISA.

Results RA patients had significantly lower DHEAS than controls (age-adjusted), in female (p<0.001) as well as in male subgroup (p=0.013). The frequency of DHEAS-related SNPs were similar in RA and control groups. In RA female patients linear regression model adjusted for age and glucocorticoid treatment, showed significant effect of risk alleles in SULT2A1 (p<0.05) and HHEX (p<0.05) genes to lowering serum DHEAS levels.

Conclusions Complex interactions exist between DHEAS-associated genotypes and adrenal androgen hypofunction in RA suggesting a significant contribution to adrenal androgen hypofunction in RA.

References

  1. Zhai G et al. Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms. PLoS Genet. 2011; 7(4):e1002025.

Acknowledgements Study was supported by VEGA 2/0018/12

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.5779

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