Lucia Vernerova1, Martina Mravcova2, Lucia Paulikova1, Miroslav Vlcek1, Andrea Marko1, Milada Meskova1, Adela Penesova1, Jozef Rovensky3, Juraj Wendl4, Katarina Raslova5, Branislav Vohnout5, Ivana Jochmanova6, Ivica Lazurova6, Zdenko Killinger7, Guenter Steiner8, Josef Smolen8, Richard Imrich1. 1. Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovakia. 2. Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovakia. martina.mravcova@savba.sk. 3. National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 01, Piestany, Slovakia. 4. NZZ Fidelitas, Liscie udolie 57, Bratislava, Slovakia. 5. Slovak Medical University, Limbova 12, 833 03, Bratislava, Slovakia. 6. 1st Department of Internal Medicine, Faculty of Medicine, Pavol Jozef Safarik University, Trieda SNP 1, 040 11, Kosice, Slovakia. 7. 5th Department of Internal Medicine, Medical Faculty of Comenius University, University Hospital Bratislava, Ruzinovska 6, 826 06, Bratislava, Slovakia. 8. Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
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.
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 RApatients. 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 RApatients and 91 healthy women. RESULTS: The allele frequencies in DHEAS-related loci were similar in RA and controls. RApatients 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 RApatients, but not in controls. Linear regression analysis showed significant effect of polymorphisms in genes ZKSCAN5 and ARPC1A on serum DHEAS levels in female RApatients 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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