TY - JOUR
T1 - Effects of polymorphisms of the sex hormone-binding globulin (SHBG) gene on free estradiol and bone mineral density
AU - Napoli, Nicola
AU - Varadharajan, Ana
AU - Rini, Giovam Batista
AU - Del Fiacco, Romano
AU - Yarramaneni, Jayasree
AU - Mumm, Steven
AU - Villareal, Dennis T.
AU - Armamento-Villareal, Reina
N1 - Funding Information:
We would like to thank Drs. Roberto Civitelli and Dwight Towler for their intellectual advice and Gerald Moskowitz PhD for his help in the urinary NTx assay. This work has been supported by NIH grants R03 AR049401 (RAV), K12 HD01459 ( Building Interdisciplinary Research Careers in Women's Health ) and the General Clinical Research Center at Washington University .
PY - 2009/12
Y1 - 2009/12
N2 - Background: Polymorphisms of the sex hormone-binding globulin (SHBG) gene are associated with differences in SHBG levels, influencing the risk for breast cancer and polycystic ovarian syndrome, but no association has been reported for osteoporosis in postmenopausal women. Objective: To determine the effect of G to A substitution in the 5′UTR (rs1799941) and the Asp356Asn (rs6259) polymorphisms of the SHBG gene on bone mineral density (BMD). Methods: This is a cross-sectional study in a university-based research center from May, 2002 to December, 2007. A total of two hundred and thirteen healthy postmenopausal Caucasian women ≥ 1 year from last menstrual period participated to this study. Serum estradiol by ultrasensitive radioimmnunoassay, serum sex hormone-binding globulin by immunoradiometric assay, and urinary NTx by enzyme-linked immunoassay were measured. BMD measurements were performed by dual energy X-ray absorptiometry and genotyping by Pyrosequencing. Results: There were no significant differences in SHBG levels associated with either rs1799941 or rs6259. Using a p value of < 0.00625 for significance, we found that subjects with the A allele (GA+AA) for the rs1799941, had a trend for lower free estradiol index (FEI) compared to the GG genotype (p = 0.04). They also had significantly lower BMD at the intertrochanter (p = 0.003) and trend for lower BMD at the total hip (p = 0.02). There was no significant difference in FEI levels between the genotypes for the rs6259 polymorphism, but women with the Asn allele (Asp/Asn+Asn/Asn), had significantly lower BMD in the total femur (p = 0.004) and intertrochanter (0.002) compared to those with the Asp/Asp genotype. Conclusions: Our data suggest that polymorphisms of the SHBG gene are associated with significant differences in BMD at the proximal femur sites. Thus, genetic variations in the SHBG gene may influence BMD at the hip in postmenopausal women.
AB - Background: Polymorphisms of the sex hormone-binding globulin (SHBG) gene are associated with differences in SHBG levels, influencing the risk for breast cancer and polycystic ovarian syndrome, but no association has been reported for osteoporosis in postmenopausal women. Objective: To determine the effect of G to A substitution in the 5′UTR (rs1799941) and the Asp356Asn (rs6259) polymorphisms of the SHBG gene on bone mineral density (BMD). Methods: This is a cross-sectional study in a university-based research center from May, 2002 to December, 2007. A total of two hundred and thirteen healthy postmenopausal Caucasian women ≥ 1 year from last menstrual period participated to this study. Serum estradiol by ultrasensitive radioimmnunoassay, serum sex hormone-binding globulin by immunoradiometric assay, and urinary NTx by enzyme-linked immunoassay were measured. BMD measurements were performed by dual energy X-ray absorptiometry and genotyping by Pyrosequencing. Results: There were no significant differences in SHBG levels associated with either rs1799941 or rs6259. Using a p value of < 0.00625 for significance, we found that subjects with the A allele (GA+AA) for the rs1799941, had a trend for lower free estradiol index (FEI) compared to the GG genotype (p = 0.04). They also had significantly lower BMD at the intertrochanter (p = 0.003) and trend for lower BMD at the total hip (p = 0.02). There was no significant difference in FEI levels between the genotypes for the rs6259 polymorphism, but women with the Asn allele (Asp/Asn+Asn/Asn), had significantly lower BMD in the total femur (p = 0.004) and intertrochanter (0.002) compared to those with the Asp/Asp genotype. Conclusions: Our data suggest that polymorphisms of the SHBG gene are associated with significant differences in BMD at the proximal femur sites. Thus, genetic variations in the SHBG gene may influence BMD at the hip in postmenopausal women.
KW - bone mineral density
KW - free estradiol
KW - osteoporosis
KW - sex hormone-binding globulin
UR - http://www.scopus.com/inward/record.url?scp=70350214361&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2009.08.001
DO - 10.1016/j.bone.2009.08.001
M3 - Article
C2 - 19679209
AN - SCOPUS:70350214361
VL - 45
SP - 1169
EP - 1174
JO - Bone
JF - Bone
SN - 8756-3282
IS - 6
ER -