What you carry at this position in your DNA and what research says about it.
Type 2 Diabetes Risk: 10/10 evidence, 59 publications.
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Sample genotype (not yours): C/C
Higher Risk of Type 2 Diabetes
Two copies of the risk allele are associated with a higher risk of developing type 2 diabetes and lower insulin secretion.
What this genotype means: Increased risk of type 2 diabetes; Decreased pancreatic insulin secretion; Slightly lower average birth weight.
Sample genotype (not yours): C/T
Moderately Increased Diabetes Risk
One copy of the risk allele is linked to a moderately elevated risk of type 2 diabetes and reduced insulin clearance.
What this genotype means: Moderately increased risk of type 2 diabetes; Reduced insulin clearance rate; Slightly lower birth weight.
Sample genotype (not yours): T/T
Typical Risk of Type 2 Diabetes
Two copies of the protective allele are associated with typical insulin secretion and baseline diabetes risk.
What this genotype means: Typical baseline risk of type 2 diabetes; Normal insulin secretion and clearance; Standard birth weight profile.
Gene function and biological role
Gene Function: The HHEX gene encodes the hematopoietically expressed homeobox protein, a transcription factor that plays a critical role in the early development of the pancreas and liver [1]. It is highly active during embryonic development, helping to guide the formation of pancreatic cells that will later produce insulin [1]. In mature adults, this gene continues to regulate pancreatic beta-cell function and insulin secretion pathways [2]. Genetic variations in and around this gene can alter its expression levels, directly impacting how efficiently the body manages blood glucose [2]. Consequently, HHEX has become one of the most widely studied and validated genetic loci in metabolic health research [3].
Variant Impact: The rs1111875 variant is an intergenic genetic change located near the HHEX gene on chromosome 10 [1]. This genetic change acts as a regulatory modifier, altering the tissue-specific enhancers that drive the expression of the HHEX protein in the pancreas [2]. When these enhancers are disrupted, pancreatic beta-cells produce less insulin in response to glucose, raising the risk of metabolic dysfunction [4]. Large-scale genomic studies across diverse global populations have consistently linked this specific variant to altered blood sugar regulation [5].
Key Insight: This genetic variant links early fetal growth to adult metabolic health, showing that the same gene regulating prenatal development also dictates adult insulin secretion.
Location: HHEX. Chromosome 10 · 10q23.33 · 92.7 Mb
Estimated prevalence by population
Global 40.8%; European 34.9%; African 59.5%; East Asian 7.9%; South Asian 18.3%; Americas 44.3%; Ashkenazi 41.1%; Finnish 27.6%; Middle Eastern 47.7%; Amish 21.5%.
Estimated CC genotype frequency.
Global 44.1%; European 48.3%; African 35.3%; East Asian 40.5%; South Asian 49.0%; Americas 44.5%; Ashkenazi 46.0%; Finnish 49.9%; Middle Eastern 42.7%; Amish 49.7%.
Estimated CT genotype frequency.
Global 15.1%; European 16.7%; African 5.2%; East Asian 51.6%; South Asian 32.8%; Americas 11.2%; Ashkenazi 12.9%; Finnish 22.5%; Middle Eastern 9.6%; Amish 28.8%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 10/10. Source: PMID 17293876. ~1.3x Higher Risk.
Insulin Secretion. Evidence: 4/10. Source: PMID 19117022. Decreased Secretion.
Metabolic Syndrome & Insulin Resistance
Insulin Clearance. Evidence: 3/10. Source: PMID 19117022. Reduced Clearance.
Endocrine & Reproductive
Pregnancy & Birth Complications
Birth Weight. Evidence: 3/10. Source: PMID 20490451. Lower Birth Weight.
Showing effects for C/T genotype
Type 2 Diabetes. Evidence: 10/10. Source: PMID 17293876. Increased Risk.
Birth Weight. Evidence: 3/10. Source: PMID 20490451. Slightly Lower.
Showing effects for T/T genotype
Type 2 Diabetes. Evidence: 10/10. Source: PMID 17293876. Typical Risk.
Insulin Secretion. Evidence: 4/10. Source: PMID 19117022. Typical Secretion.
Insulin Clearance. Evidence: 3/10. Source: PMID 19117022. Typical Clearance.
Birth Weight. Evidence: 3/10. Source: PMID 20490451. Typical Birth Weight.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Carrying two copies of the C allele significantly increases the risk of developing type 2 diabetes over your lifetime [1]. This genetic predisposition is primarily driven by a reduction in the first and second phases of insulin secretion from pancreatic beta-cells [2]. Because your body produces less insulin in response to glucose, managing blood sugar levels requires more conscious effort [2]. Additionally, this genotype is associated with reduced insulin clearance, meaning insulin remains in circulation longer but is less effective [2]. Interestingly, this variant also links adult metabolic health to early development, as individuals with this genotype tend to have slightly lower birth weights [3]. Maintaining a balanced diet and regular physical activity is highly recommended to offset this genetic risk [4].
Increased risk of type 2 diabetes; Decreased pancreatic insulin secretion; Slightly lower average birth weight.
Sample genotype: CT (Heterozygous)
Carrying one copy of the C allele places you in an intermediate risk category for metabolic health challenges [1]. Research indicates that heterozygous carriers experience a moderate reduction in early-phase insulin secretion following meals [2]. This genotype is also specifically associated with reduced insulin clearance, which can affect how your body processes and degrades insulin [2]. Because insulin is a vital growth factor in the womb, carrying this risk allele is also associated with a minor reduction in birth weight [3]. While your risk is lower than those with two copies of the risk allele, proactive lifestyle habits remain beneficial [4]. Regular exercise and a diet low in refined sugars can help maintain optimal insulin sensitivity and support long-term metabolic health [4].
Moderately increased risk of type 2 diabetes; Reduced insulin clearance rate; Slightly lower birth weight.
Sample genotype: TT (Homozygous)
Carrying two copies of the T allele means you do not carry the risk-associated variant for this specific genetic marker [1]. Your body is expected to have typical pancreatic beta-cell development and normal phases of insulin secretion [2]. Because you lack the risk allele, you do not experience the genetic reduction in insulin clearance or secretion seen in carriers [2]. Your genetic predisposition for birth weight is also typical, reflecting standard prenatal growth patterns [3]. While this genotype provides a favorable baseline, overall metabolic health is still heavily influenced by lifestyle factors [4]. Maintaining a balanced diet and staying active will help preserve your natural metabolic efficiency [4].
Typical baseline risk of type 2 diabetes; Normal insulin secretion and clearance; Standard birth weight profile.
Variants with shared genetic architecture
rs5015480 · HHEX Gene · Chr 10 · Type 2 Diabetes Risk
rs7923837 · HHEX Gene · Chr 10 · Type 2 Diabetes Risk
rs10811661 · CDKN2B Gene · Chr 9 · Type 2 Diabetes Risk
Content updated August 2026.
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