Dataset Information

Circulating testosterone and SHBG concentrations are heritable in women: the Framingham Heart Study.

ABSTRACT: Many factors influence the concentration of circulating testosterone and its primary binding protein, SHBG. However, little is known about the genetic contribution to their circulating concentrations in women, and their heritability in women is not well established.Our objective was to estimate the heritability of circulating total testosterone (TT), free testosterone (FT), and SHBG in women in families from the Framingham Heart Study.Women in the Framingham Heart Study who were not pregnant, had not undergone bilateral oophorectomy, and were not using exogenous hormones were eligible for this investigation. TT was measured using liquid chromatography tandem mass spectrometry and SHBG using an immunofluorometric assay (Delfia-Wallac), and FT was calculated. Heritability estimates were calculated using variance-components methods in Sequential Oligogenic Linkage Analysis Routines (SOLAR) and were adjusted for age, age(2), body mass index (BMI), BMI(2), diabetes, smoking, and menopausal status. Bivariate analyses were done to assess genetic correlation between TT, FT, and SHBG.A total of 2685 women were studied including 868 sister pairs and 688 mother-daughter pairs. Multivariable adjusted heritability estimates were 0.26 ± 0.05 for FT, 0.26 ± 0.05 for TT, and 0.56 ± 0.05 for SHBG (P < 1.0 × 10(-7) for all). TT was genetically correlated with SHBG [genetic correlation coefficient (?G) = 0.31 ± 0.10] and FT (?G = 0.54 ± 0.09), whereas SHBG was inversely correlated with FT (?G = -0.60 ± 0.08).Circulating TT, FT, and SHBG concentrations in women are significantly heritable, underscoring the importance of further work to identify the specific genes that contribute significantly to variation in sex steroid concentrations in women. The strong shared genetic component among pairs of TT, FT, and SHBG concentrations suggests potential pleiotropic effects for some of the underlying genes.

SUBMITTER: Coviello AD

PROVIDER: S-EPMC3167671 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Circulating testosterone and SHBG concentrations are heritable in women: the Framingham Heart Study.

Coviello A D AD Zhuang W V WV Lunetta K L KL Bhasin S S Ulloor J J Zhang A A Karasik D D Kiel D P DP Vasan R S RS Murabito J M JM

The Journal of clinical endocrinology and metabolism 20110713 9

<h4>Context</h4>Many factors influence the concentration of circulating testosterone and its primary binding protein, SHBG. However, little is known about the genetic contribution to their circulating concentrations in women, and their heritability in women is not well established.<h4>Objective</h4>Our objective was to estimate the heritability of circulating total testosterone (TT), free testosterone (FT), and SHBG in women in families from the Framingham Heart Study.<h4>Methods</h4>Women in th ...[more]

PMID: 21752884

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Project description:Background A higher circulating plasma ceramide ratio (C16:0/C24:0) is associated with an increased risk of heart failure, even after accounting for standard risk factors including lipid markers. However, the pathobiological mechanisms that underlie this association are incompletely understood. We tested the hypothesis that plasma ceramide ratio (C16:0/C24:0) is associated with adverse cardiac remodeling in the community. Methods and Results We evaluated 2652 Framingham Offspring Study participants (mean age, 66±9 years; 55% women) who attended their eighth examination cycle and underwent routine echocardiography and liquid chromatography-tandem mass spectrometry-based assays for circulating ceramide concentrations. We used multivariable linear regression models to relate C16:0/C24:0 (independent variable) to the following echocardiographic measures (dependent variables; separate models for each): left ventricular mass, left ventricular ejection fraction, left atrial emptying fraction, left atrial end-systolic volume, E/e' (a measure of left ventricular diastolic function), and left ventricular global circumferential and longitudinal strain by speckle-tracking echocardiography. In multivariable-adjusted analyses, higher C16:0/C24:0 per standard deviation increment was associated with lower left ventricular ejection fraction (0.991-fold change in left ventricular ejection fraction; P=0.0004), worse global circumferential strain (?=0.34, P=0.004), higher left atrial end-systolic volume (?=2.48, p<0.0001), and lower left atrial emptying fraction (0.99-fold change; P<0.0001). The C16:0/C24:0 ratio was not associated with either E/e' or global longitudinal strain, and the association with higher left ventricular mass was rendered statistically nonsignificant upon correction for multiple comparisons. Conclusions Our cross-sectional observations in a large community-based sample are consistent with a potential detrimental impact of higher ceramide ratio (C16:0/24:0) on cardiac remodeling traits, which may partly explain the associations of these molecular species with clinical heart failure.

Project description:Background Limited data are available on the prospective relationship between beverage consumption and plasma lipid and lipoprotein concentrations. Two major sources of sugar in the US diet are sugar-sweetened beverages (SSBs) and 100% fruit juices. Low-calorie sweetened beverages are common replacements. Methods and Results Fasting plasma lipoprotein concentrations were measured in the FOS (Framingham Offspring Study) (1991-2014; N=3146) and Generation Three (2002-2001; N=3584) cohorts. Beverage intakes were estimated from food frequency questionnaires and grouped into 5 intake categories. Mixed-effect linear regression models were used to examine 4-year changes in lipoprotein measures, and Cox proportional hazard models were used to estimate hazard ratios for incident dyslipidemia, adjusting for potential confounding factors. We found that regular (>1 serving per day) versus low (<1 serving per month) SSB consumption was associated with a greater mean decrease in high-density lipoprotein cholesterol (β±standard error -1.6±0.4 mg/dL; Ptrend<0.0001) and increase in triglyceride (β±standard error: 4.4±2.2 mg/dL; Ptrend=0.003) concentrations. Long-term regular SSB consumers also had a higher incidence of high triglyceride (hazard ratio, 1.52; 95% CI, 1.03-2.25) compared with low consumers. Although recent regular low-calorie sweetened beverage consumers had a higher incidence of high non-high-density lipoprotein cholesterol (hazard ratio, 1.40; 95% CI, 1.17-1.69) and low-density lipoprotein cholesterol (hazard ratio, 1.27; 95% CI, 1.05-1.53) concentrations compared with low consumers, cumulative average intakes of low-calorie sweetened beverages were not associated with changes in non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol concentrations, or incident dyslipidemias. Conclusions SSB intake was associated with adverse changes in high-density lipoprotein cholesterol and triglyceride concentrations, along with a higher risk of incident dyslipidemia, suggesting that increased SSB consumption may contribute to the development of dyslipidemia.

Dataset Information

Circulating testosterone and SHBG concentrations are heritable in women: the Framingham Heart Study.

Publications

Circulating testosterone and SHBG concentrations are heritable in women: the Framingham Heart Study.

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