Abstract
Objective
Lower production of adrenal androgens has been confirmed in females with rheumatoid arthritis (RA); however, the mechanisms of this finding are not completely understood. The aim of our study was to assess the contribution of genetic factors associated with variability of dehydroepiandrosterone sulfate (DHEAS) levels to lower DHEAS in female RA patients.
Methods
448 RA and 648 healthy controls were genotyped for single-nucleotide polymorphisms (SNPs) in genes ZKSCAN5 (rs11761528), SULT2A1 (rs2637125), HHEX (rs2497306), and ARPC1A (rs740160). Serum DHEAS concentrations were measured in 112 RA patients and 91 healthy women.
Results
The allele frequencies in DHEAS-related loci were similar in RA and controls. RA patients had significantly lower serum DHEAS concentrations compared to healthy women. The cumulative number of alleles associated with lower DHEAS within genes ZKSCAN5, SULT2A1, HHEX, and ARPC1A present in each individual negatively correlated with DHEAS levels in RA patients, but not in controls. Linear regression analysis showed significant effect of polymorphisms in genes ZKSCAN5 and ARPC1A on serum DHEAS levels in female RA patients but not in the control group.
Conclusion
Our findings suggest that complex interactions exist between genotype and adrenal androgen hypofunction in RA.
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Acknowledgements
We would like to thank all collaborating rheumatologists from Slovakia for contribution to sample collection (Zuzana Cizmarikova, Nadezda Rovderova, Bohuslav Dobrovodsky, Zlata Kmecova, Anna Mankova, Maria Mihaleova, Maria Oetterova, Marcela Palova, Maria Palasthyova, Eva Strakova, Erika Timanikova, Anna Scipova).
Funding
This work was supported by the grants ATMOS N00024 and VEGA 2/0161/16.
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The authors’ responsibilities were as follow: L.V. and M.Mr. contributed equally to this work; R.I. conceived and designed the study; J.R., J.W., K.R., B.V., I.J., I.L., Z.K., G.S., and J.S. contributed to sample collection; L.V., M.Mr., L.P., M.V., M.Me., A.M. A.P., R.I. contributed to data collection and data analysis; L.V., M.Mr., M.V., and R.I. wrote the manuscript; L.V., M.Mr., M.V., and R.I. researched data, contributed to the discussion. All authors reviewed and edited the manuscript.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Lucia Vernerova and Martina Mravcova are joint first authors.
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Vernerova, L., Mravcova, M., Paulikova, L. et al. Contribution of Genetic Factors to Lower DHEAS in Patients with Rheumatoid Arthritis. Cell Mol Neurobiol 38, 379–383 (2018). https://doi.org/10.1007/s10571-017-0522-0
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DOI: https://doi.org/10.1007/s10571-017-0522-0