title: The CYP19 gene and associations with androgens and abdominal obesity in premenopausal women.
abstract: OBJECTIVE
  Elevated androgens in women are associated with type 2 diabetes and are dependent on the conversion to estrogens by aromatase cytochrome P450. Polymorphisms of a tetranucleotide repeat [TTTA](n) in the fourth intron of the CYP19 gene are associated with endocrine-dependent diseases and were examined in relation to hormone levels and disease risk factors in premenopausal women.
  
  
  METHODS
  A population sample of women born in 1956 (n = 270) were genotyped for this polymorphism and the results set in relation to steroid hormones, including saliva cortisol, anthropometric variables, estimates of insulin, glucose and lipid metabolism, and blood pressure.
  
  
  RESULTS
  Seven tetranucleotide repeat [TTTA](n) alleles were detected with allelic sizes of 168 to 195 bp, with a TCT deletion/insertion (168/171 bp) upstream of this microsatellite. Smoking was associated with elevated androgens (p = 0.005 to 0.019). Using the median (average stretch, 177.5 bp) as a dividing line, nonsmoking women with the shorter microsatellite had higher free testosterone (p = 0.018) and lower sex hormone binding globulin (p = 0.033). These differences were pronounced with the 168-bp allele. Such women were also characterized by a less-substantial decrease of morning cortisols ("unwinding"; p = 0.035) and central obesity (abdominal sagittal diameter, p = 0.049) and had waist/hip circumference ratios of borderline significance (p = 0.064).
  
  
  CONCLUSIONS
  The results indicate that, in premenopausal women, a short microsatellite in the fourth intron of the CYP19 gene, caused by a TCT deletion upstream the [TTTA](n) tract, is associated with elevated androgens, perturbed regulation of the hypothalamic-pituitary-adrenal axis, and abdominal obesity.
authors.affiliation: The Cardiovascular Institute, Sahlgrenska University Hospital, Göteborg, Sweden. fariba.baghaei@hjl.gu.se
authors.forename: Fariba
authors.initials: F
authors.lastname: Baghaei
authors.forename: Roland
authors.initials: R
authors.lastname: Rosmond
authors.forename: Lars
authors.initials: L
authors.lastname: Westberg
authors.forename: Monica
authors.initials: M
authors.lastname: Hellstrand
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
authors.forename: Göran
authors.initials: G
authors.lastname: Holm
authors.forename: Per
authors.initials: P
authors.lastname: Björntorp
mesh_terms: D000005:Abdomen; D000311:Adrenal Glands / Q000503:physiopathology; D000328:Adult; D000483:Alleles; D000728:Androgens / Q000097:blood*; D001141:Aromatase / Q000235:genetics*; D001824:Body Constitution; D002940:Circadian Rhythm; D015331:Cohort Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007031:Hypothalamus / Q000503:physiopathology; D007438:Introns / Q000235:genetics; D018895:Microsatellite Repeats; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D010902:Pituitary Gland / Q000503:physiopathology; D011110:Polymorphism, Genetic; D017697:Premenopause; D012463:Saliva / Q000737:chemistry; D017384:Sequence Deletion; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood
chemical_list: D000728:Androgens; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D001141:Aromatase; D006854:Hydrocortisone