Dataset Information

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

ABSTRACT: 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.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).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 > or = 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.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.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.

SUBMITTER: Napoli N

PROVIDER: S-EPMC3689651 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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

Napoli Nicola N Varadharajan Ana A Rini Giovam Batista GB Del Fiacco Romano R Yarramaneni Jayasree J Mumm Steven S Villareal Dennis T DT Armamento-Villareal Reina R

Bone 20090811 6

<h4>Background</h4>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.<h4>Objective</h4>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).<h4>Methods</h4>This is a cross-sectional s ...[more]

PMID: 19679209

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Project description:BackgroundSex hormones are recognized to play a significant role in increasing bone mineral density (BMD) and promoting bone maturation during adolescence. The purpose of our study was to use a database with large population data to evaluate the association of BMD with sex hormones (including testosterone and estradiol) and sex hormone-binding globulin (SHBG) in adolescent boys and girls aged 12-19 years.MethodsThe data for our study were taken from the National Health and Nutrition Examination Survey 2013-2016, and we used weighted multiple linear regression models to assess the relationship between testosterone, estradiol, and SHBG and total BMD. We use weighted generalized additive models and smooth curve fitting to discover underlying nonlinear relationships.ResultsA total of 1648 teenagers (853 boys, 795 girls) were selected for the final analysis. In boys, testosterone and estradiol levels were positively associated with total BMD, whereas SHBG levels were negatively associated with total BMD after adjusting for covariates [P < 0.05; 95% confidence interval (CI)]. In addition, there was a point between estradiol and total BMD, after which the positive correlation between estradiol and total BMD was relatively insignificant in boys. In girls, there was a positive association between estradiol and total BMD (P < 0.05; 95% CI), but there was no significant association between the testosterone (β 0.0004; 95% CI -0.0001 to 0.0008) or SHBG (β -0.0001; 95% CI -0.0002 to 0.0001) levels and total BMD. We also found an inverted U-shaped association between testosterone and total BMD with the inflection point at 25.4 ng/dL of testosterone.ConclusionsWe found differences in the association of sex hormones with total BMD in boys and girls. Based on our findings, an appropriate increase in serum testosterone levels may be beneficial for skeletal development in girls because of the inverted U-shaped relationship (with the inflection point at 25.4 ng/dL of testosterone), and a high testosterone level might be detrimental to BMD. Furthermore, keeping estradiol levels below a certain level in boys (24.3 pg/mL) may be considered.

Project description:Background and Purpose- Circulating levels of SHBG (sex hormone-binding globulin) have been inversely linked to obesity, diabetes mellitus, and other cardiometabolic disorders. It remains uncertain whether low SHBG is prospectively predictive of stroke risk, particularly in women. We investigated whether SHBG is associated with risk of incident ischemic stroke (IS) among women in the WHI (Women's Health Initiative). Methods- From an observational cohort of 161 808 postmenopausal women enrolled in the WHI at 40 sites across the United States from 1993 to 1998, we identified 13 192 participants free of prevalent stroke at baseline who were included in an ancillary study that measured serum SHBG. We used Cox proportional hazards regression, stratified by SHBG measurement assay, to assess IS risk across quintiles of SHBG (Q1-Q5), adjusting first for demographic variables (model 1), additionally for body mass index, hypertension, alcohol use, and smoking status (model 2), and for physical activity and reproductive risk factors (model 3). In sensitivity analyses, potential mediators (diabetes mellitus status, levels of estradiol, testosterone, and CRP [C-reactive protein]) were included. Results- Of 13 192 participants (mean age, 62.5 years; 67.4% non-Hispanic white, 18.5% black, 7.6% Hispanic, and 5.0% Asian), after following for an average of 11.6 years, 768 IS events were adjudicated. Compared with the highest quintile of SHBG levels (referent), women in the lowest SHBG quintile had a higher risk of IS in all 3 multivariable models (model 1: hazard ratio, 1.88 [95% CI, 1.47-2.41]; model 2: hazard ratio, 1.69 [95% CI, 1.30-2.20]; model 3: hazard ratio, 1.61 [95% CI, 1.19-2.19]; trend tests P<0.05 for all models). Including potential mediators such as diabetes mellitus, estradiol, and testosterone in the models attenuated but did not eliminate significant inverse associations between SHBG and IS. Conclusions- In this prospective cohort of postmenopausal women, there was a statistically significant inverse association between serum SHBG levels and IS risk, which supports the notion that SHBG could be used as a risk stratification tool for predicting IS in women.

Dataset Information

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

Publications

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

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