title: Genetics of neuroendocrine factors in rheumatoid arthritis.
abstract: 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.
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Mravcova
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: L
authors.initials: L
authors.lastname: Chovanova
authors.affiliation: Center for Molecular Medicine, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: L
authors.initials: L
authors.lastname: Paulikova
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Vlcek
authors.affiliation: National Institute of Rheumatic Diseases, Piestany, Slovakia.
authors.forename: J
authors.initials: J
authors.lastname: Rovensky
authors.affiliation: 5th Department of Internal Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Z
authors.initials: Z
authors.lastname: Killinger
authors.affiliation: Fidelitas, s.r.o., Rheumatology Out-patient Clinic, Bratislava, Slovakia.
authors.forename: J
authors.initials: J
authors.lastname: Wendl
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: R
authors.initials: R
authors.lastname: Imrich
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D015238:Sulfotransferases / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C078492:HHEX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D006854:Hydrocortisone