title: Association of genetic variants in the two isoforms of 5α-reductase, SRD5A1 and SRD5A2, in lean patients with polycystic ovary syndrome.
abstract: OBJECTIVE
  Given its role in converting testosterone to dihydrotestosterone and cortisol to dihydrocortisol, 5α-reductase may be important in the pathophysiology of the polycystic ovary syndrome (PCOS). Increased activity of this enzyme has already been demonstrated in ovaries of affected women, and might be caused by genetic alterations. The aim of this study was to analyze representative genetic variants of both isoforms of 5α-reductase with regard to PCOS parameters in lean and obese women.
  
  
  METHODS
  We analyzed one single nucleotide polymorphism (SNP) (rs523349) of the isoform 2 (SRD5A2) and one haplotype of the isoform 1 (SRD5A1), consisting of the two SNPs rs39848 and rs3797179, in 249 women with PCOS and 226 healthy women using a 5'-exonuclease-assay. The genotypes were associated with anthropometric, metabolic and hormonal as well as functional tests in these women.
  
  
  RESULTS
  In the investigated haplotype of SRD5A1, the TA variant was associated with an increased frequency of PCOS (P=0.022) and an increased Ferriman-Gallwey Score (hirsutism) (P=0.016) in women with normal weight. The G allele at the examined position of the SRD5A2 showed a decreased frequency of PCOS (P=0.03) in women with normal weight.
  
  
  CONCLUSIONS
  One of the keys in the development of the PCOS is hyperandrogenism, which might be caused by an increased 5α-reductase activity, as it is often seen in obesity. This mechanism might therefore be of importance in lean PCOS patients and contribute to the clinical findings.
authors.affiliation: Department of Endocrinology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. matthias.graupp@stud.medunigraz.at
authors.forename: M
authors.initials: M
authors.lastname: Graupp
authors.forename: E
authors.initials: E
authors.lastname: Wehr
authors.forename: N
authors.initials: N
authors.lastname: Schweighofer
authors.forename: T R
authors.initials: TR
authors.lastname: Pieber
authors.forename: B
authors.initials: B
authors.lastname: Obermayer-Pietsch
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000328:Adult; D001835:Body Weight / Q000235:genetics; D016022:Case-Control Studies; D042944:Cholestenone 5 alpha-Reductase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D009765:Obesity / Q000453:epidemiology / Q000235:genetics; D011085:Polycystic Ovary Syndrome / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D013851:Thinness / Q000453:epidemiology / Q000235:genetics*
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D042944:Cholestenone 5 alpha-Reductase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548467:SRD5A1 protein, human; C548468:SRD5A2 protein, human