title: Common genetic variants of the human steroid 21-hydroxylase gene (CYP21A2) are related to differences in circulating hormone levels.
abstract: OBJECTIVE
  Systematic evaluation of the potential relationship between the common genetic variants of CYP21A2 and hormone levels.
  
  
  METHODS
  The relationships of CYP21A2 intron 2 polymorphisms and haplotypes with diverse baseline and stimulated blood hormone levels were studied in 106 subjects with non-functioning adrenal incidentaloma (NFAI). The rationale for using NFAI subjects is dual: i) their baseline hormone profiles do not differ from those of healthy subjects and ii) hormone levels after stimulation tests are available.
  
  
  RESULTS
  The carriers (N = 27) of a well-defined CYP21A2 haplotype cluster (c5) had significantly elevated levels of cortisol (p = 0.0110), and 17-hydroxyprogesterone (p = 0.0001) after ACTH stimulation, and 11-deoxycortisol after metyrapone administration (p = 0.0017), but the hormone values were in normal ranges. In addition, the carriers (N = 33) of the C allele of the rs6462 polymorphism had a higher baseline aldosterone level (p = 0.0006). The prevalence of these genetic variants of CYP21A2 did not differ between NFAI and healthy subjects.
  
  
  CONCLUSIONS
  The common CYP21A2 variants presumably exert the same effect on hormone levels in the healthy and disease-affected populations. Therefore, they may contribute to complex diseases such as some cardiovascular diseases, and may influence the genotype-phenotype correlation in patients with congenital adrenal hyperplasia (CAH) including the individual need for hormone substitution.
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary; Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Márton
authors.initials: M
authors.lastname: Doleschall
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Julianna Anna
authors.initials: JA
authors.lastname: Szabó
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Júlia
authors.initials: J
authors.lastname: Pázmándi
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Szilágyi
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary; "Lendület" Hereditary Endocrine Tumours Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Klára
authors.initials: K
authors.lastname: Koncz
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Henriette
authors.initials: H
authors.lastname: Farkas
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Tóth
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Igaz
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Edit
authors.initials: E
authors.lastname: Gláz
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
authors.affiliation: Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary; 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Károly
authors.initials: K
authors.lastname: Rácz
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: George
authors.initials: G
authors.lastname: Füst
authors.affiliation: Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary; "Lendület" Hereditary Endocrine Tumours Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Patócs
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood*; D000236:Adenoma / Q000097:blood / Q000235:genetics; D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood / Q000235:genetics; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011899:Ranitidine; D012189:Retrospective Studies; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D019326:17-alpha-Hydroxyprogesterone; D011899:Ranitidine; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase; D006854:Hydrocortisone