The CYP19 gene and associations with androgens and abdominal obesity in premenopausal women.
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.
Baghaei
Fariba
F
The Cardiovascular Institute, Sahlgrenska University Hospital, Göteborg, Sweden. fariba.baghaei@hjl.gu.se
Rosmond
Roland
R
Westberg
Lars
L
Hellstrand
Monica
M
Eriksson
Elias
E
Holm
Göran
G
Björntorp
Per
P
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
D000728:Androgens; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D001141:Aromatase; D006854:Hydrocortisone