What you carry at this position in your DNA and what research says about it.
SHBG and Metabolism: 9/10 evidence, 28 publications.
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Sample genotype (not yours): T/T
Lower SHBG Levels and Higher Metabolic Risk
Two copies of the T allele are associated with a significant reduction in sex hormone-binding globulin levels. This reduction is linked to a higher waist-to-hip ratio and increased metabolic susceptibility.
What this genotype means: Reduced SHBG levels; Higher waist-to-hip ratio; Increased risk of type 2 diabetes.
Sample genotype (not yours): C/C
Typical SHBG Levels and Favorable Metabolic Profile
Two copies of the C allele support typical levels of sex hormone-binding globulin. This genetic profile is associated with a healthier body fat distribution and lower metabolic risk.
What this genotype means: Typical SHBG levels; Favorable waist-to-hip ratio; Lower risk of type 2 diabetes.
Sample genotype (not yours): T/C
Slightly Lower SHBG Levels and Moderate Metabolic Risk
One copy of the T allele is linked to a moderate decrease in sex hormone-binding globulin. This intermediate state slightly increases the likelihood of abdominal fat storage and metabolic variations.
What this genotype means: Slightly reduced SHBG levels; Slightly higher waist-to-hip ratio; Modestly increased metabolic risk.
Gene function and biological role
Gene Function: The SHBG gene encodes sex hormone-binding globulin, a crucial protein produced by the liver that regulates the bioavailability of sex steroids [1]. By binding tightly to testosterone and estradiol, this carrier protein controls how much hormone is free to enter tissues and exert biological effects [1]. Circulating levels of this protein are highly variable and serve as an important marker for metabolic health [2]. Low levels are frequently associated with insulin resistance, weight gain, and an elevated risk of metabolic disorders [2].
Variant Impact: Located near the SHBG gene, the rs727428 variant is one of the strongest genetic determinants of circulating sex hormone-binding globulin levels [1]. The genetic change alters the expression of the SHBG protein, directly influencing how much carrier protein is released into the bloodstream [1]. A reduction in these carrier levels subsequently increases the proportion of active, unbound sex hormones [2]. This shift in hormone availability is closely linked to downstream changes in body fat distribution and lipid metabolism [2].
Key Insight: This variant is a major genetic driver of how your body distributes fat, acting through the regulation of active sex hormone levels rather than direct metabolic pathways.
Location: SHBG. Chromosome 17 · 17p13.1 · 7.6 Mb
Estimated prevalence by population
Global 21.1%; European 18.3%; African 27.0%; East Asian 24.8%; South Asian 36.2%; Americas 15.1%; Ashkenazi 25.3%; Finnish 14.1%; Middle Eastern 17.5%; Amish 20.9%.
Estimated TT genotype frequency.
Global 49.0%; European 49.0%; African 49.9%; East Asian 50.0%; South Asian 47.9%; Americas 47.5%; Ashkenazi 50.0%; Finnish 46.9%; Middle Eastern 48.7%; Amish 49.6%.
Estimated TC genotype frequency.
Global 30.0%; European 32.8%; African 23.0%; East Asian 25.2%; South Asian 15.8%; Americas 37.3%; Ashkenazi 24.7%; Finnish 39.0%; Middle Eastern 33.8%; Amish 29.5%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Endocrine & Reproductive
Hormone Levels & Endocrine Regulation
SHBG Levels. Evidence: 9/10. Source: PMID 22675492. Reduced Levels.
Cardiovascular & Metabolic
Obesity & Body Composition
Waist-to-Hip Ratio. Evidence: 8/10. Source: PMID 30239722. Increased Ratio.
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 8/10. Source: PMID 38374256. Increased Risk.
Lipids & Cholesterol
Triglycerides. Evidence: 6/10. Source: PMID 30275531. Increased Levels.
Showing effects for C/C genotype
SHBG Levels. Evidence: 9/10. Source: PMID 22675492. Typical Levels.
Waist-to-Hip Ratio. Evidence: 8/10. Source: PMID 30239722. Typical Ratio.
Type 2 Diabetes. Evidence: 8/10. Source: PMID 38374256. Typical Risk.
Triglycerides. Evidence: 6/10. Source: PMID 30275531. Typical Levels.
Showing effects for T/C genotype
SHBG Levels. Evidence: 9/10. Source: PMID 22675492. Slightly Reduced.
Waist-to-Hip Ratio. Evidence: 8/10. Source: PMID 30239722. Slightly Increased.
Type 2 Diabetes. Evidence: 8/10. Source: PMID 38374256. Slightly Increased.
Triglycerides. Evidence: 6/10. Source: PMID 30275531. Slightly Increased.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Two copies of the T allele lead to an approximate 27% reduction in circulating sex hormone-binding globulin levels [1]. Because this protein binds and inactivates sex hormones, lower levels result in a higher fraction of free, active hormones in the bloodstream [1]. This hormonal imbalance is strongly associated with an increased waist-to-hip ratio and abdominal fat accumulation [2]. Clinical studies have linked this specific genetic profile to higher HbA1c levels and elevated triglycerides, which are key indicators of metabolic strain [3]. Furthermore, the reduction in SHBG is a recognized risk factor for the development of type 2 diabetes [4]. Men with this genotype may also face a higher risk of hypogonadism due to altered hormone regulation [5]. Maintaining a balanced diet and regular physical activity can help mitigate these genetically influenced metabolic risks.
Reduced SHBG levels; Higher waist-to-hip ratio; Increased risk of type 2 diabetes.
Sample genotype: CC (Homozygous)
Possessing two copies of the C allele is associated with the highest and most stable levels of circulating sex hormone-binding globulin [1]. Adequate levels of this carrier protein ensure proper regulation of active testosterone and estrogen in the bloodstream [1]. This balanced hormonal state is linked to a lower waist-to-hip ratio, reflecting a healthier distribution of body fat [2]. Individuals with this genotype typically exhibit favorable metabolic markers, including lower baseline triglycerides and stable HbA1c levels [3]. The presence of typical SHBG levels also provides a protective effect against insulin resistance and type 2 diabetes [4]. Furthermore, this genotype is associated with a lower risk of male hypogonadism, supporting overall endocrine health [5]. These genetic advantages provide a strong foundation for maintaining long-term metabolic and cardiovascular wellness.
Typical SHBG levels; Favorable waist-to-hip ratio; Lower risk of type 2 diabetes.
Sample genotype: TC (Heterozygous)
Inheriting one T allele and one C allele results in an intermediate phenotype, characterized by an approximate 13% reduction in sex hormone-binding globulin levels [1]. This moderate decrease in the carrier protein slightly elevates the levels of active, unbound sex hormones circulating in the body [1]. Consequently, this genotype is associated with a mild increase in waist-to-hip ratio and a tendency toward abdominal fat distribution [2]. Research indicates subtle elevations in metabolic markers such as HbA1c and triglycerides compared to the typical genotype [3]. The overall impact on type 2 diabetes risk is modest but present, reflecting the close relationship between SHBG and insulin sensitivity [4]. While the genetic influence is moderate, lifestyle factors remain the primary driver of metabolic outcomes. Regular cardiovascular exercise and a fiber-rich diet are highly effective strategies to support healthy hormone binding and metabolic function.
Slightly reduced SHBG levels; Slightly higher waist-to-hip ratio; Modestly increased metabolic risk.
Variants with shared genetic architecture
rs1799941 · SHBG Gene · Chr 17 · Hormone Binding Globulin
rs6258 · SHBG Gene · Chr 17 · Hormone Binding Globulin
rs12150660 · SHBG Gene · Chr 17 · Testosterone and Hormone Balance
A cross-population atlas of genetic associations for 220 human phenotypes.
Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.
Content updated August 2026.
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