Our findings suggest that complex interactions exist between genotype and adrenal androgen hypofunction in RA.
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 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
Inadequate production of cortisol related to inflammation and decrease in adrenal androgen production are hallmarks of hypothalamic-pituitary-adrenal (HPA)-related endocrine findings in rheumatoid arthritis (RA). In particular, lower dehydroepiandrosterone sulfate (DHEAS) levels were consistently found in a subset of premenopausal RA females. Recently, several new gene variants have been identified in association with serum DHEAS concentrations, such as in SULT2A1 and HHEX genes. These DHEAS-related genes and other variants involved in HPA regulation may play a role in the adrenal androgen deficiency in RA. The aim of our study was to review involvement of genetic mechanisms of HPA regulation, with focus on adrenal androgens, in the context of RA pathophysiology. Although, effects of the DHEAS-related gene variants appear to be relatively small compared to other well-known factors such as age, complex interactions between DHEAS-associated genotypes and adrenal androgen hypofunction phenotype may exist in RA. Further studies analyzing specific neuroendocrine phenotype/genotype in RA are needed.
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