Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies.

Background: Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably.

Objectives: We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components.

Data Sources: Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE.

Synthesis and regulation of sex hormone-binding globulin in obesity.

Sex hormone-binding globulin (SHBG) is a plasma glycoprotein with high binding affinity for testosterone and dihydrotestosterone and lower affinity for estradiol. SHBG is synthesized in the liver, and its plasma level is important in the regulation of plasma free and albumin-bound androgens and estrogens. Obesity and particularly excess visceral fat, known risk factors for cardiovascular and metabolic diseases, are associated with decreased testosterone levels in males and SHBG levels in both sexes.

Baroreflex sensitivity and variants of the renin angiotensin system genes.

Objectives: Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations between baroreflex sensitivity (BRS) and polymorphism in the RAS genes.

Background: Wide intersubject variability in BRS is not well explained by cardiovascular risk factors or life style, suggesting a genetic component responsible for the variation of BRS.

Methods: Baroreflex sensitivity as measured from the overshoot phase of the Valsalva maneuver and genetic polymorphisms were examined in a random sample of 161 women and 154 men aged 41 to 61 years and then in an independent random cohort of 29 men and 37 women aged 36 to 37 years.

Joint effects of an aldosterone synthase (CYP11B2) gene polymorphism and classic risk factors on risk of myocardial infarction.

Background: The -344C allele of a 2-allele (C or T) polymorphism in the promoter of the gene encoding aldosterone synthase (CYP11B2) is associated with increased left ventricular size and mass and with decreased baroreflex sensitivity, known risk factors for morbidity and mortality associated with myocardial infarction (MI). We hypothesized that this polymorphism was a risk factor for MI.

Methods And Results: We used a nested case-control design to investigate the relationships between this polymorphism and the risk of nonfatal MI in 141 cases and 270 matched controls from the Helsinki Heart Study, a coronary primary prevention trial in dyslipidemic, middle-aged men.

Aldosterone synthase (CYP11B2) polymorphisms and cardiovascular function.

In addition to regulating renal sodium resorption and, thus, intravascular volume, aldosterone may have direct effects on the cardiovascular system. We previously identified a polymorphism (-344C/T) in the promoter of the aldosterone synthase (CYP11B2) gene that affects binding of the SF-1 transcription factor and thus might influence gene expression. We found that, whereas this polymorphism has inconsistent associations with levels of aldosterone secretion and blood pressure, the -344C allele is strongly associated with increased left ventricular size and decreased baroreflex sensitivity in healthy individuals.