Genetic polymorphisms are associated with serum levels of sex hormone binding globulin in postmenopausal women.
BACKGROUND
Estrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues. The objective of this study was to analyze the influence of common polymorphisms of the SHBG gene on serum SHBG, bone mineral density (BMD), and osteoporotic fractures.


METHODS
Four biallelic polymorphisms of the SHBG gene were studied by means of Taqman assays in 753 postmenopausal women. BMD was measured by DXA and serum SHBG was measured by ELISA.


RESULTS
Age, body weight, and two polymorphisms of the SHBG gene (rs6257 and rs1799941 [A/G]) were significantly associated with serum SHBG in unadjusted and age- and weight-adjusted models. Alleles at the rs1799941 locus showed the strongest association with serum SHBG (p=0.0004). The difference in SHBG levels between women with AA and GG genotypes at the rs1799941 locus was 39%. There were no significant differences in BMD across SHBG genotypes. The genotypes showed similar frequency distributions in control women and women with vertebral or hip fractures.


CONCLUSIONS
Some common genetic variants of the SHBG gene, and particularly an A/G polymorphism situated in the 5' region, influence serum SHBG levels. However, a significant association with BMD or osteoporotic fractures has not been demonstrated.
Riancho
José A
JA
Department of Internal Medicine, Hospital UM Valdecilla-IFIMAV, University of Cantabria, Santander, Spain. rianchoj@unican.es
Valero
Carmen
C
Zarrabeitia
María T
MT
García-Unzueta
María T
MT
Amado
José A
JA
González-Macías
Jesús
J
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015519:Bone Density / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000097:blood / Q000235:genetics*; D012738:Sex Hormone-Binding Globulin / Q000235:genetics*
D012738:Sex Hormone-Binding Globulin