What you carry at this position in your DNA and what research says about it.
Bilirubin and Gallstones: 8/10 evidence, 21 publications.
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Sample genotype (not yours): C/C
Typical Bilirubin and Lower Gallstone Risk
Typical bilirubin levels and a lower risk of developing gallstones are associated with this genotype. It is also linked to slightly higher LDL and total cholesterol levels.
What this genotype means: Typical bilirubin levels; Lower risk of gallstones; Slightly higher LDL cholesterol.
Sample genotype (not yours): C/T
Slightly Elevated Bilirubin and Gallstone Risk
Slightly higher bilirubin levels and a minor increase in gallstone risk are common with this genotype. Cholesterol levels are typically in the normal range.
What this genotype means: Slightly elevated bilirubin; Slightly higher gallstone risk; Typical cholesterol levels.
Sample genotype (not yours): T/T
Elevated Bilirubin and Higher Gallstone Risk
Elevated bilirubin levels, often characteristic of Gilbert's syndrome, and a higher risk of gallstones are linked to this genotype. It is also associated with slightly lower cholesterol levels.
What this genotype means: Elevated bilirubin levels; Higher risk of gallstones; Slightly lower LDL cholesterol.
Gene function and biological role
Gene Function: The UGT1A10 gene belongs to the UDP-glucuronosyltransferase family, which plays a critical role in the detoxification and elimination of various foreign and endogenous compounds. It is part of a complex gene cluster on chromosome 2 that also encodes UGT1A1, the primary enzyme responsible for metabolizing bilirubin [1]. Enzymes in this family perform glucuronidation, a process that attaches a sugar molecule to toxins, drugs, and hormones to make them water-soluble for excretion. Although UGT1A10 is primarily expressed in the gastrointestinal tract, variants in this region are often in tight linkage disequilibrium with UGT1A1 variants, directly influencing systemic bilirubin levels [2].
Variant Impact: The rs4148325 variant is an intronic change located within the UGT1A gene cluster on chromosome 2. This genetic marker is highly correlated with the classic UGT1A1*28 promoter variant, which reduces the expression of the glucuronidation enzyme [2]. Because of this strong genetic linkage, carrying the T allele at rs4148325 serves as a reliable proxy for reduced enzyme activity and slower clearance of bilirubin [2]. Consequently, individuals with the T allele tend to have higher levels of circulating unconjugated bilirubin in their blood [1]. This elevation is typically benign but can increase the risk of developing pigment-based gallstones over time [3].
Key Insight: Although elevated bilirubin is linked to gallstones, it is also associated with lower LDL and total cholesterol levels.
Location: UGT1A1. Chromosome 2 · 2q37.1 · 233.8 Mb
Estimated prevalence by population
Global 41.3%; European 46.2%; African 30.4%; East Asian 76.4%; South Asian 34.8%; Americas 45.6%; Ashkenazi 38.3%; Finnish 33.3%; Middle Eastern 44.9%; Amish 33.3%.
Estimated CC genotype frequency.
Global 45.1%; European 43.6%; African 49.5%; East Asian 22.0%; South Asian 48.4%; Americas 43.9%; Ashkenazi 47.2%; Finnish 48.8%; Middle Eastern 44.2%; Amish 48.8%.
Estimated CT genotype frequency.
Global 13.6%; European 10.3%; African 20.1%; East Asian 1.6%; South Asian 16.9%; Americas 10.5%; Ashkenazi 14.5%; Finnish 17.9%; Middle Eastern 10.9%; Amish 17.9%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Organ Systems
Liver Function & Disease
Bilirubin Levels. Evidence: 8/10. Source: PMID 21646302. Typical.
Digestive & Gut Disorders
Gallstones. Evidence: 8/10. Source: PMID 34651315. Lower Risk.
Gallbladder Inflammation. Evidence: 6/10. Source: PMID 39024449. Typical Risk.
Cardiovascular & Metabolic
Lipids & Cholesterol
Cholesterol Levels. Evidence: 6/10. Source: PMID 39024449. Slightly Higher.
Pharmacogenomics
Immunosuppressant & Biologic Response
Sarilumab Response. Evidence: 3/10. Source: PMID 35149777. Typical Response.
Showing effects for C/T genotype
Bilirubin Levels. Evidence: 8/10. Source: PMID 21646302. Slightly Elevated.
Gallstones. Evidence: 8/10. Source: PMID 34651315. Slightly Higher Risk.
Gallbladder Inflammation. Evidence: 6/10. Source: PMID 39024449. Slightly Higher Risk.
Cholesterol Levels. Evidence: 6/10. Source: PMID 39024449. Typical.
Sarilumab Response. Evidence: 3/10. Source: PMID 35149777. Moderate Elevation.
Showing effects for T/T genotype
Bilirubin Levels. Evidence: 8/10. Source: PMID 21646302. Elevated.
Gallstones. Evidence: 8/10. Source: PMID 34651315. Higher Risk.
Gallbladder Inflammation. Evidence: 6/10. Source: PMID 39024449. Higher Risk.
Cholesterol Levels. Evidence: 6/10. Source: PMID 39024449. Slightly Lower.
Sarilumab Response. Evidence: 3/10. Source: PMID 35149777. Higher Elevation.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Efficient clearance of bilirubin from the bloodstream is characteristic of the C/C genotype, which maintains fully functional glucuronidation enzymes [1]. Because bilirubin is processed normally, there is a lower likelihood of it crystallizing into pigment gallstones in the gallbladder [2]. This genotype also protects against gallbladder inflammation, known as cholecystitis [2]. On the other hand, large-scale genetic data shows that the C allele is associated with slightly higher total and LDL cholesterol levels [2]. When treated with certain medications like sarilumab, typical bilirubin levels are maintained without the benign spikes seen in T allele carriers [3]. This baseline metabolic profile ensures standard processing of various drugs and environmental toxins. Maintaining a balanced diet and regular exercise can help manage the slightly higher cholesterol levels associated with this genotype.
Typical bilirubin levels; Lower risk of gallstones; Slightly higher LDL cholesterol.
Sample genotype: CT (Heterozygous)
A single copy of the T allele mildly reduces the efficiency of bilirubin glucuronidation [1]. This mild reduction often leads to slightly elevated levels of unconjugated bilirubin in the blood, though usually well within a safe range [1]. Because of the minor increase in circulating bilirubin, there is a slightly higher risk of developing pigment gallstones [2]. This genotype is also associated with a small increase in the risk of gallbladder inflammation [2]. Interestingly, the presence of one T allele balances out the cholesterol-raising effect of the C allele, resulting in typical LDL and total cholesterol levels [2]. If treated with the anti-inflammatory drug sarilumab, moderate, benign increases in bilirubin may occur that do not indicate liver damage [3]. Standard liver function tests will easily distinguish these benign genetic elevations from actual liver injury.
Slightly elevated bilirubin; Slightly higher gallstone risk; Typical cholesterol levels.
Sample genotype: TT (Homozygous)
Significantly reduced activity of the UGT1A1 enzyme occurs in individuals with the T/T genotype due to strong genetic linkage with the UGT1A1*28 variant [1]. This reduction in enzyme function slows down the processing of bilirubin, leading to elevated levels of unconjugated bilirubin in the blood [2]. This condition, often referred to as Gilbert's syndrome, is generally harmless and does not signify liver disease [1]. However, the excess bilirubin in the bile can precipitate, leading to a higher risk of developing pigment gallstones and gallbladder inflammation [3]. On the positive side, this genotype is associated with slightly lower total and LDL cholesterol levels [3]. Additionally, if treated with medications like sarilumab, pronounced but benign spikes in bilirubin levels are highly likely [1]. Knowing this genetic status helps prevent unnecessary medical concern over elevated bilirubin results on routine blood panels.
Elevated bilirubin levels; Higher risk of gallstones; Slightly lower LDL cholesterol.
Variants with shared genetic architecture
rs6742078 · UGT1A1 Gene · Chr 2 · Gallstone Risk
rs887829 · UGT1A1 Gene · Chr 2 · Bilirubin and Heart Health
rs10929302 · UGT1A1 Gene · Chr 2 · Drug and Bilirubin Clearance
Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
Content updated August 2026.
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