Polymorphisms in the P450 c17 (17-hydroxylase/17,20-Lyase) and P450 c19 (aromatase) genes: association with serum sex steroid concentrations and bone mineral density in postmenopausal women.
The CYP 17 and CYP 19 genes encode 17alpha-hydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. We investigated the association between 2 common polymorphisms in 1) the promoter region (T-->C substitution) of CYP 17, and 2) exon 3 (G-->A) of CYP 19, bone mineral density (BMD) and serum androgen/estradiol, in a case-control study of 252 postmenopausal women aged 64.5 +/- 9.2 yr (mean +/- SD). There was no significant difference in serum estradiol concentrations between cases (n = 136) and controls (n = 116). The CYP 19 genotype was significantly associated with serum estradiol (P = 0.002). Women with the AA genotype had higher serum estradiol concentrations compared with those with the GG genotype (P = 0.03). In older women, those with the CYP 19 GA and GG genotypes had an increased prevalence of osteoporosis (P = 0.04) and fractures (P = 0.003). We found no significant association between CYP 17 genotype and serum androgens and estradiol concentrations. However, a significant association was seen between BMD values at the femoral neck with CYP 17 genotype in cases (P = 0.04) and in the whole study population (P = 0.012). Subjects with the CC genotype had significantly lower BMD (mean +/- SD: TT, 0.7 +/- 0.16; CC, 0.6 +/- 0.08 g/cm(2); P = 0.006). In conclusion, both CYP 17 and CYP 19 are candidate genes for osteoporosis in postmenopausal women.
Somner
John
J
Department of Chemical Pathology, St. Thomas' Hospital, London, SE1 7EH United Kingdom.
McLellan
Susan
S
Cheung
Joseph
J
Mak
Y T
YT
Frost
Michelle L
ML
Knapp
Karen M
KM
Wierzbicki
Anthony S
AS
Wheeler
Michael
M
Fogelman
Ignac
I
Ralston
Stuart H
SH
Hampson
Geeta N
GN
D000368:Aged; D001141:Aromatase / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D016022:Case-Control Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000097:blood; D005091:Exons / Q000235:genetics; D005260:Female; D005272:Femur Neck; D005787:Gene Frequency; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011401:Promoter Regions, Genetic / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D013739:Testosterone / Q000097:blood
D012739:Gonadal Steroid Hormones; D013739:Testosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase