Effects of polymorphisms of the sex hormone-binding globulin (SHBG) gene on free estradiol and bone mineral density

Nicola Napoli, Ana Varadharajan, Giovam Batista Rini, Romano Del Fiacco, Jayasree Yarramaneni, Steven Mumm, Dennis T. Villareal, Reina Armamento-Villareal

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1169-1174
Number of pages6
JournalBone
Volume45
Issue number6
DOIs
Publication statusPublished - Dec 2009

Fingerprint

Sex Hormone-Binding Globulin
Bone Density
Estradiol
Genes
Genotype
Femur
Hip
Alleles
Immunoradiometric Assay
Serum Globulins
Postmenopausal Osteoporosis
Polycystic Ovary Syndrome
Photon Absorptiometry
Viperidae
Immunoenzyme Techniques
Cross-Sectional Studies
Breast Neoplasms
Serum
Research

Keywords

  • bone mineral density
  • free estradiol
  • osteoporosis
  • sex hormone-binding globulin

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Napoli, N., Varadharajan, A., Rini, G. B., Del Fiacco, R., Yarramaneni, J., Mumm, S., ... Armamento-Villareal, R. (2009). Effects of polymorphisms of the sex hormone-binding globulin (SHBG) gene on free estradiol and bone mineral density. Bone, 45(6), 1169-1174. https://doi.org/10.1016/j.bone.2009.08.001

Effects of polymorphisms of the sex hormone-binding globulin (SHBG) gene on free estradiol and bone mineral density. / Napoli, Nicola; Varadharajan, Ana; Rini, Giovam Batista; Del Fiacco, Romano; Yarramaneni, Jayasree; Mumm, Steven; Villareal, Dennis T.; Armamento-Villareal, Reina.

In: Bone, Vol. 45, No. 6, 12.2009, p. 1169-1174.

Research output: Contribution to journalArticle

Napoli, N, Varadharajan, A, Rini, GB, Del Fiacco, R, Yarramaneni, J, Mumm, S, Villareal, DT & Armamento-Villareal, R 2009, 'Effects of polymorphisms of the sex hormone-binding globulin (SHBG) gene on free estradiol and bone mineral density', Bone, vol. 45, no. 6, pp. 1169-1174. https://doi.org/10.1016/j.bone.2009.08.001
Napoli N, Varadharajan A, Rini GB, Del Fiacco R, Yarramaneni J, Mumm S et al. Effects of polymorphisms of the sex hormone-binding globulin (SHBG) gene on free estradiol and bone mineral density. Bone. 2009 Dec;45(6):1169-1174. https://doi.org/10.1016/j.bone.2009.08.001
Napoli, Nicola ; Varadharajan, Ana ; Rini, Giovam Batista ; Del Fiacco, Romano ; Yarramaneni, Jayasree ; Mumm, Steven ; Villareal, Dennis T. ; Armamento-Villareal, Reina. / Effects of polymorphisms of the sex hormone-binding globulin (SHBG) gene on free estradiol and bone mineral density. In: Bone. 2009 ; Vol. 45, No. 6. pp. 1169-1174.
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abstract = "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.",
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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

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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.

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