What is the Origin of SHBG Gene Variation?

The concept stems from molecular endocrinology and pharmacogenomics, where researchers identified that genetic differences in the SHBG locus contribute to the substantial inter-individual variability observed in SHBG serum concentrations. These genetic studies have elucidated a key non-gonadal determinant of sex hormone action.

What is the Mechanism of SHBG Gene Variation?

A specific gene variation can affect the transcription rate of the SHBG gene, leading to constitutively higher or lower baseline production of the protein by the hepatocytes. Alternatively, a variation may alter the structure of the SHBG protein itself, potentially affecting its binding affinity for steroid hormones. A lower circulating SHBG concentration, for example, results in a higher fraction of free testosterone, which can lead to clinical signs of androgen excess despite normal total testosterone levels.

SHBG Gene Variation

Meaning

SHBG Gene Variation refers to polymorphisms or single nucleotide polymorphisms (SNPs) within the gene encoding Sex Hormone-Binding Globulin (SHBG), which result in alterations to the protein’s structure, synthesis rate, or circulating concentration. SHBG is a critical glycoprotein synthesized primarily by the liver that binds and transports sex steroid hormones, including testosterone and estradiol, thereby regulating their bioavailability to target tissues. Genetic variations in the SHBG gene can significantly impact an individual’s free, biologically active hormone levels, influencing clinical phenotypes related to fertility, metabolism, and cancer risk.