What you carry at this position in your DNA and what research says about it.
Diabetes Risk: 8/10 evidence, 10 publications.
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Sample genotype (not yours): T/T
Higher Type 2 Diabetes Risk
This genotype is associated with an increased risk of developing type 2 diabetes and slightly higher average blood sugar levels. It provides a typical baseline risk for type 1 diabetes.
What this genotype means: Increased risk of type 2 diabetes; Slightly higher average HbA1c levels; Typical baseline risk for type 1 diabetes.
Sample genotype (not yours): G/G
Lowest Type 2 but Highest Type 1 Diabetes Risk
This genotype offers the strongest genetic protection against type 2 diabetes but carries the highest risk for type 1 diabetes. It also correlates with a poorer response to DPP-4 inhibitors.
What this genotype means: Lowest risk of type 2 diabetes; Highest genetic risk for type 1 diabetes; Poorer response to DPP-4 inhibitor medications.
Sample genotype (not yours): T/G
Mixed Diabetes Risk and Lower Drug Response
This genotype presents a genetic trade-off, showing a lower risk for type 2 diabetes alongside an increased risk for type 1 diabetes. It is also linked to a reduced response to certain diabetes medications.
What this genotype means: Lower risk of type 2 diabetes; Increased risk of type 1 diabetes; Reduced response to DPP-4 inhibitor medications.
Gene function and biological role
Gene Function: The CTRB1 gene encodes chymotrypsinogen B1, a digestive enzyme produced by the pancreas that plays an unexpected role in glucose metabolism [1]. Alongside the neighboring CTRB2 gene, it influences the incretin pathway, which stimulates insulin secretion after eating [1]. This gene locus is highly active in pancreatic tissues and helps regulate how the body responds to blood sugar fluctuations [1]. Variations in this region can alter the expression of these enzymes, directly impacting pancreatic beta-cell function and insulin release [2]. Understanding this gene helps clarify the biological links between exocrine pancreatic function and endocrine glucose control [1] [2].
Variant Impact: The rs7202877 variant is an intergenic genetic marker located near the CTRB1 and CTRB2 genes on chromosome 16 [1]. This specific change influences the expression levels of chymotrypsin enzymes in the pancreas, which in turn affects insulin secretion stimulated by the hormone GLP-1 [1]. The major T allele is associated with reduced pancreatic gene expression and lower insulin release, elevating the risk of metabolic issues [1] [2]. Conversely, the minor G allele increases CTRB1 and CTRB2 expression, enhancing insulin secretion but also altering immune-related susceptibility pathways [1] [3]. This dual effect makes the variant a key genetic pivot between different metabolic and autoimmune conditions [1] [3].
Key Insight: This variant acts as a genetic trade-off, where the allele that protects against type 2 diabetes simultaneously increases the risk for type 1 diabetes.
Location: CTRB1. Chromosome 16 · 16q23.1 · 75.2 Mb
Estimated prevalence by population
Global 76.2%; European 80.7%; African 67.2%; East Asian 63.7%; South Asian 85.0%; Americas 80.4%; Ashkenazi 85.3%; Finnish 74.1%; Middle Eastern 88.8%; Amish 77.7%.
Estimated TT genotype frequency.
Global 22.0%; European 18.3%; African 29.5%; East Asian 32.2%; South Asian 14.4%; Americas 18.6%; Ashkenazi 14.1%; Finnish 24.0%; Middle Eastern 10.9%; Amish 20.9%.
Estimated TG genotype frequency.
Global 1.8%; European 1.0%; African 3.2%; East Asian 4.1%; South Asian 0.6%; Americas 1.1%; Ashkenazi 0.6%; Finnish 1.9%; Middle Eastern 0.3%; Amish 1.4%.
Estimated GG genotype frequency.
Showing effects for T/T genotype
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 8/10. Source: PMID 22885922. ~1.12x Higher Risk.
Type 1 Diabetes. Evidence: 5/10. Source: PMID 19430480. Typical Risk.
HbA1c. Evidence: 6/10. Source: PMID 33462484. Slightly Higher.
Pharmacogenomics
Diabetes Medication Response
DPP-4 Inhibitor Response. Evidence: 5/10. Source: PMID 23674605. Typical Response.
Showing effects for G/G genotype
Type 2 Diabetes. Evidence: 8/10. Source: PMID 22885922. Lowest Risk.
Type 1 Diabetes. Evidence: 5/10. Source: PMID 19430480. Highest Risk.
HbA1c. Evidence: 6/10. Source: PMID 33462484. Typical.
DPP-4 Inhibitor Response. Evidence: 5/10. Source: PMID 23674605. Poorer Response.
Showing effects for T/G genotype
Type 2 Diabetes. Evidence: 8/10. Source: PMID 22885922. Lower Risk.
Type 1 Diabetes. Evidence: 5/10. Source: PMID 19430480. ~1.28x Higher Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Carrying two copies of the T allele is linked to a moderately increased susceptibility to type 2 diabetes [1]. Large-scale genetic studies show an odds ratio of approximately 1.12 for developing the condition compared to carriers of the G allele [1] [2]. This increased risk appears to stem from impaired insulin release, particularly during the phase of insulin secretion stimulated by the incretin hormone GLP-1 [3]. Biomarker data also links this genotype to slightly higher HbA1c levels, reflecting higher average blood sugar over time [4]. On the positive side, this genotype does not carry the genetic risk factor for type 1 diabetes associated with this locus [5]. Additionally, individuals with this genotype show a typical, standard response to DPP-4 inhibitor medications used to manage blood sugar [3].
Increased risk of type 2 diabetes; Slightly higher average HbA1c levels; Typical baseline risk for type 1 diabetes.
Sample genotype: GG (Homozygous)
Carrying two copies of the G allele represents the most pronounced genetic trade-off at this locus [1]. This genotype is highly protective against type 2 diabetes, driven by significantly enhanced pancreatic expression of the CTRB1 and CTRB2 genes [2]. This increased expression leads to higher chymotrypsin activity and a substantial boost in insulin secretion following meals [2]. However, this genetic profile also carries the highest risk for type 1 diabetes, an autoimmune condition where the body attacks its own insulin-producing cells [1] [3]. Additionally, individuals with this genotype are more likely to have a poorer response to DPP-4 inhibitor therapies, meaning alternative blood sugar medications may be preferred if treatment is ever required [2]. Regular health check-ups can help monitor these contrasting metabolic tendencies.
Lowest risk of type 2 diabetes; Highest genetic risk for type 1 diabetes; Poorer response to DPP-4 inhibitor medications.
Sample genotype: TG (Heterozygous)
Inheriting one copy of the G allele creates a complex metabolic profile with opposing risks [1]. On one hand, the G allele is protective against type 2 diabetes, as it is associated with a 33% increase in GLP-1 stimulated insulin secretion and higher pancreatic expression of CTRB1 and CTRB2 [2]. On the other hand, this same G allele is a recognized risk factor for type 1 diabetes, increasing susceptibility to this autoimmune condition with an odds ratio of about 1.28 [1]. Furthermore, clinical studies suggest that G allele carriers may experience a poorer therapeutic response to DPP-4 inhibitors, a common class of blood-sugar-lowering medications [2]. This means that while the body naturally secretes insulin more efficiently, medical management of diabetes using specific drugs might be less effective [2]. Maintaining a balanced lifestyle remains key to managing these intersecting metabolic influences.
Lower risk of type 2 diabetes; Increased risk of type 1 diabetes; Reduced response to DPP-4 inhibitor medications.
Variants with shared genetic architecture
rs11257655 · CDC123 Gene · Chr 10 · Type 2 Diabetes Risk
rs1799884 · GCK Gene · Chr 7 · Blood Sugar and Diabetes Risk
rs2796441 · TLE1-DT Gene · Chr 9 · Type 2 Diabetes Risk
The CTRB1/2 locus affects diabetes susceptibility and treatment via the incretin pathway.
Genetics of 35 blood and urine biomarkers in the UK Biobank.
Type 1 diabetes: etiology, immunology, and therapeutic strategies.
Content updated August 2026.
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