scholarly journals Sex-specific Associations of Sex Hormone Binding Globulin with CKD and Kidney Function: A Univariable and Multivariable Mendelian Randomization Study in the UK Biobank

2020 ◽  
pp. ASN.2020050659
Author(s):  
Jie V. Zhao ◽  
C. Mary Schooling
Keyword(s):  
Kidney Function ◽  
Lower Risk ◽  
Mendelian Randomization ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Nucleotide Polymorphisms ◽  
Hormone Binding ◽  
Shbg Level ◽  
The Uk ◽  
Sex Disparity

BackgroundKidney function declines faster in men. Testosterone levels may mediate the sex disparity. Correspondingly, levels of sex hormone binding globulin (SHBG), which modulates sex hormones, might also be relevant to the lower kidney function in men. The sex-specific role of SHBG is unclear.MethodsA sex-specific, Mendelian randomization (MR) study provided unconfounded estimates of SHBG levels among the United Kingdom Biobank population. Univariable MR applied 357 single nucleotide polymorphisms (SNPs) in men and 359 SNPs in women. These published SNPs strongly (P<5×10−8) predict SHBG level. They were profiled in 179,916 white British men (6016 patients with CKD) and 212,079 white British women (5958 patients with CKD), to obtain the effect of SHBG on CKD, albuminuria, and eGFR. Multivariable MR controlling for testosterone was used to assess the effect of SHBG on CKD and kidney function independent of testosterone in men.ResultsGenetically predicted higher SHBG was associated with a lower risk of CKD in men (odds ratio [OR], 0.78 per SD; 95% confidence interval [95% CI], 0.65 to 0.93) but had no benefit in women. The effect in men remained in multivariable MR, allowing for testosterone (OR, 0.61; 95% CI, 0.45 to 0.82).ConclusionsGenetically predicted higher SHBG was associated with a lower risk of CKD and better kidney function in men, but not in women, suggesting that SHBG may play a role in CKD specifically in men. Identifying drivers of SHBG and the underlying pathways could provide new insights into CKD prevention and treatment.

scholarly journals Genetically predicted sex hormone binding globulin and ischemic heart disease in men and women: a univariable and multivariable Mendelian randomization study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie V. Zhao ◽  
C. Mary Schooling
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Mendelian Randomization ◽  
Sex Hormone ◽  
Ischemic Heart ◽  
Sex Hormone Binding Globulin ◽  
Inverse Association ◽  
Hormone Binding ◽  
The Uk

AbstractMen are more vulnerable to ischemic heart disease (IHD) than women, possibly due to testosterone. Correspondingly, sex hormone binding globulin (SHBG) which lowers circulating testosterone might protect men against IHD. SHBG may also affect IHD independent of testosterone, which has not previously been examined. To assess the sex-specific role of SHBG in IHD, in univariable Mendelian randomization (MR), we used sex-specific, genome-wide significant genetic variants to predict SHBG, and examined their association with IHD in the UK Biobank. We also replicated using genetic instruments from Japanese men and applied to Biobank Japan. To assess the role of SHGB independent of testosterone in men, we used multivariable MR controlling for testosterone. Genetically predicted SHBG was associated with lower IHD risk in men [odds ratio (OR) 0.78 per standard deviation, 95% confidence interval (CI) 0.70 to 0.87], and the association was less clear in women. The estimates were similar in Japanese. The inverse association remained after controlling for testosterone in men (OR 0.79, 95% CI 0.71 to 0.88). SHBG might lower the risk of IHD in men, with a role independent of testosterone. Exploring intervention strategies that increase SHBG is important for targeting IHD treatments.

scholarly journals The relationship between components of metabolic syndrome and plasma level of sex hormone-binding globulin

2019 ◽  
Vol 29 (2) ◽  
Author(s):  
Amin Alinezhad ◽  
Fatemeh Jafari
Keyword(s):  
Metabolic Syndrome ◽  
Plasma Level ◽  
Lipid Profiles ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Metabolic Abnormalities ◽  
Hormone Binding ◽  
Men And Women ◽  
Shbg Level ◽  
The Relationship

Plasma concentration of sex hormone-binding globulin (SHBG), as an androgen binding protein, is impressed by many physiological and environmental factors. Recent studies have shown that plasma level of SHBG is related to some components of metabolic syndrome (MetS); however, in contrast, few articles failed to show any associations between SHBG and MetS. So, this study was conducted to investigate the relationship between Components of Metabolic Syndrome and Plasma Level of Sex Hormone-Binding Globulin. In this study, after measuring the plasma level of SHBG in 84 individuals, the relation between MetS and the plasma level of SHBG was investigated. After evaluating the plasma level of SHBG and metabolic abnormalities in men and women, we investigated the factors which mentioned above in two groups including patients with and without MetS. Also, the metabolic abnormalities which evaluated in this study including plasma level of 25-hydroxyvitamin D, serum uric acid (SUA), Albumin, lipid profiles and etc. according to five components of MetS. Our result shows that SHBG could contributed to some laboratory parameters such as LDL-C (P<0.05), total cholesterol (P<0.05), triglycerides (P<0.05) and etc. in men, but not in women. On the other hand, we observed that concentration of SHBG is higher in patients with MetS (P<0.05); however, results from our experiment showed that there is no relation between lower level of SHBG and five components of MetS such as central obesity, raised fasting plasma glucose (FPG) (P>0.05), reduced HDL-C (P>0.05), raised triglycerides (P>0.05) and raised blood pressure (P>0.05) in both men and women. There is a significant association between SHBG and Log-Hip Circumference (P<0.05), Non-HDL-C (P<0.05) and Log-25(OH)D (P<0.05) was seen in this cross-section study in both men and women. Results obtained from our study suggest that SHBG is not a powerful enough factor to use as a predictor of MetS alone and there is no association between plasma level of SHBG and development of five components of MetS, however, lower SHBG level may contributed to lipid profiles.

scholarly journals Statistical Genomic Approach Identifies Association between FSHR Polymorphisms and Polycystic Ovary Morphology in Women with Polycystic Ovary Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Tao Du ◽  
Yu Duan ◽  
Kaiwen Li ◽  
Xiaomiao Zhao ◽  
Renmin Ni ◽  
...  
Keyword(s):  
Polycystic Ovary ◽  
Follicle Stimulating Hormone ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Nucleotide Polymorphisms ◽  
Hormone Binding ◽  
Functional Variants ◽  
Fshr Gene ◽  
Genomic Approach ◽  
Stimulating Hormone

Background.Single-nucleotide polymorphisms (SNPs) in the follicle stimulating hormone receptor (FSHR) gene are associated with PCOS. However, their relationship to the polycystic ovary (PCO) morphology remains unknown. This study aimed to investigate whether PCOS related SNPs in the FSHR gene are associated with PCO in women with PCOS.Methods. Patients were grouped into PCO (n=384) and non-PCO (n=63) groups. Genomic genotypes were profiled using Affymetrix human genome SNP chip 6. Two polymorphisms (rs2268361 and rs2349415) of FSHR were analyzed using a statistical approach.Results. Significant differences were found in the allele distributions of the GG genotype of rs2268361 between the PCO and non-PCO groups (27.6% GG, 53.4% GA, and 19.0% AA versus 33.3% GG, 36.5% GA, and 30.2% AA), while no significant differences were found in the allele distributions of the GG genotype of rs2349415. When rs2268361 was considered, there were statistically significant differences of serum follicle stimulating hormone, estradiol, and sex hormone binding globulin between genotypes in the PCO group. In case of the rs2349415 SNP, only serum sex hormone binding globulin was statistically different between genotypes in the PCO group.Conclusions. Functional variants in FSHR gene may contribute to PCO susceptibility in women with PCOS.

Abstract 011: Sex Hormone-Binding Globulin (SHBG) and Risk of Clinical Diabetes in American Black, Hispanic, and Asian/Pacific Islander Postmenopausal Women.

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Brian H Chen ◽  
Kathleen Brennan ◽  
Atsushi Goto ◽  
Yiqing Song ◽  
Najib Aziz ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Mendelian Randomization ◽  
Diabetes Risk ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Clinical Diabetes ◽  
Hormone Binding ◽  
Mendelian Randomization Analysis ◽  
Asian Pacific ◽  
Randomization Analysis

BACKGROUND: Recent prospective studies have shown a strong inverse association between sex hormone-binding globulin (SHBG) levels and risk of clinical diabetes in Whites. However, it remains unknown whether this relation extends to other racial/ethnic populations. METHODS: We evaluated the association between baseline levels of SHBG and risk of clinical diabetes in the Women’s Health Initiative Observational Study. Over a median follow-up of 5.9 years, 542 postmenopausal women developed clinical diabetes (338 Blacks, 128 Hispanics, 76 Asians) and were matched to 1,110 controls (707 Blacks, 249 Hispanics, 154 Asians). To complement our protein-level findings, we also genotyped 5 SHBG polymorphisms. We performed Mendelian randomization analysis to assess the potential causal relation between SHBG levels and risk of clinical diabetes. RESULTS: Overall, higher levels of SHBG at baseline were associated with a significantly lower risk of clinical diabetes (Relative risk [RR]=0.24, 95% confidence interval [CI]=0.15-0.39 for highest versus lowest quartile of SHBG, adjusted for BMI and other known diabetes risk factors). The associations remained consistent across ethnic groups (p-for-heterogeneity=0.72): RR=0.29 (95%CI=0.16-0.54) for Blacks, RR=0.26 (95%CI=0.09-0.74) for Hispanics, and RR=0.32 (95%CI=0.06-1.73) for Asians, comparing highest to lowest quartiles of SHBG. In addition, SHBG polymorphisms affected diabetes risk proportional to serum SHBG levels. Mendelian randomization analysis confirmed the significant direct effect of SHBG on diabetes development (p=0.03). CONCLUSIONS: In this prospective cohort of postmenopausal women, we observed a robust, inverse relation between serum levels of SHBG and clinical diabetes risk in American Blacks, Hispanics, and Asian/Pacific Islanders. Genetic variants associated with SHBG levels demonstrated a similar relationship, providing support for a causal role of SHBG in the pathogenesis of type 2 diabetes.

scholarly journals Sex hormone-binding globulin predicts the incidence of hyperglycemia in women: interactions with adiponectin levels

2009 ◽  
Vol 161 (1) ◽  
pp. 81-85 ◽  
Author(s):  
F Bonnet ◽  
B Balkau ◽  
J M Malécot ◽  
P Picard ◽  
C Lange ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Conditional Logistic Regression ◽  
Insulin Resistance Syndrome ◽  
Study Data ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
High Fasting Glucose ◽  
Shbg Level ◽  
Nested Case Control

ObjectivePrevious evidence has suggested that a low sex hormone-binding globulin (SHBG) concentration is associated with insulin-resistance and a low adiponectin concentration. We investigated the association between SHBG and the risk of hyperglycemia in each sex and we determined potential interactions between SHBG and adiponectin levels in the development of dysglycemia.DesignWe used a nested case–control design in the large prospective study, Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR). We studied 227 men and women who were normoglycemic at baseline but hyperglycemic at 3 years (glycemia≥6.1 mmol/l or type 2 diabetes). They were matched for sex, age, and body mass index with 227 subjects who remained normoglycemic at 3 years.ResultsAt baseline, the concentration of SHBG was significantly lower in women who subsequently developed hyperglycemia than in those who remained normoglycemic, with no difference for men. In multiple regression, SHBG at baseline was as an independent determinant of plasma adiponectin levels, in both women (P<0.0001) and men (P=0.002). In multivariate conditional logistic regression taking into account physical activity and changes in waist circumference over the follow-up, plasma SHBG remained significantly associated with the development of hyperglycemia in women but not in men. These associations persisted after adjustment for fasting insulinemia, high fasting glucose, and adiponectin levels.ConclusionsThese findings suggest that a low SHBG level is a strong risk marker for dysglycemia in women, independently of both adiponectinemia and insulinemia. SHBG may therefore improve the identification of women at risk of diabetes.

scholarly journals Sex hormone-binding globulin and arthritis: a Mendelian randomization study

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Zihao Qu ◽  
Jiawei Huang ◽  
Fangkun Yang ◽  
Jianqiao Hong ◽  
Wei Wang ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding
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