Gilbert Syndrome: Mildly Raised Bilirubin From a Common Gene Variant

Table of Contents

1. A Slower Liver Enzyme, Not a Liver Disease
2. The Gene Variants Behind It
3. How Common It Is, Population by Population
4. Symptoms, and Their Frequent Absence
5. What Pushes Bilirubin Higher
6. How It Is Identified
7. Medicines Affected by Slower UGT1A1
8. Raised Bilirubin and the Heart: Observational Findings
9. Gallstones, Lungs, Athletes and Other Associations
10. How It Differs From Crigler-Najjar Syndrome
11. What Is Not Known
12. Key Research Papers
13. Connections
14. Featured Videos

A Slower Liver Enzyme, Not a Liver Disease

Bilirubin leaves the blood in two steps. First it travels to the liver in its "unconjugated" (also called indirect) form, which does not dissolve in water. The liver then attaches a sugar-acid group to it — a step called glucuronidation — turning it into "conjugated" (direct) bilirubin that can pass into bile and out of the body. The enzyme that does this is uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1). A 1995 study in the New England Journal of Medicine described it as the only enzyme that contributes substantially to bilirubin glucuronidation, and reported that in people with Gilbert syndrome the liver's glucuronidating activity is reduced to about 30 percent of normal (Bosma 1995).

The result is a mild, long-lasting rise in unconjugated bilirubin "in the absence of liver disease or overt hemolysis," in the words of that study — that is, without liver damage and without the excess red-cell destruction that is the other common cause of a high unconjugated bilirubin. A review in the European Journal of Pediatrics calls it a benign condition for which no specific management is necessary (Fretzayas 2012), and a clinical reference review states that it does not require treatment and that the outlook is excellent (Grant 2024). The condition is also known in Europe as Gilbert-Meulengracht syndrome (Strassburg 2010). It was described in the early 1900s by Augustin Gilbert and colleagues (Grant 2024).

Sources describe its inheritance in two ways. The clinical reference review and the Egyptian cohort study call it autosomal recessive — it shows when both copies of the gene carry the slow variant (Grant 2024; Kamal 2019). The pediatric review calls it autosomal dominant with incomplete penetrance (Fretzayas 2012). The difference reflects a real complexity covered in the next section: carrying the variant on both copies is usual in people with the syndrome, but not everyone who carries it has raised bilirubin.

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The Gene Variants Behind It

The best-known cause is a tiny change not in the enzyme itself but in the "switch" region (promoter) that controls how much enzyme is made. In 1995, researchers in Amsterdam sequenced the UGT1A1 gene in 10 unrelated people with Gilbert syndrome. The part of the gene that codes for the enzyme was normal in all 10. Instead, every one of them carried two extra letters (TA) in the promoter on both copies of the gene — a sequence written A(TA)7TAA instead of the usual A(TA)6TAA. In liver cancer cells grown in the laboratory, the longer version reduced the output of a reporter gene (Bosma 1995). This longer promoter is the variant now called UGT1A1*28, and the pediatric review names the homozygous *28 genotype as the most common genotype in Gilbert syndrome (Fretzayas 2012).

The same study found the longer version on 40 percent of gene copies among 55 people without the syndrome. Only the 3 men who carried it on both copies had significantly higher bilirubin than the other 52. The authors concluded that the promoter change "appears to be necessary for Gilbert's syndrome but not sufficient for the complete manifestation of the syndrome" (Bosma 1995).

Other variants matter in other populations. In Japan, a 1998 laboratory study modelled a change in the enzyme itself, G71R (glycine to arginine at position 71). A model carrying G71R on both copies had 32.2 percent of normal UGT1A1 activity — the level seen in Gilbert syndrome — while a model carrying it on one copy had 60.2 percent (Yamamoto 1998). This change is the variant labelled UGT1A1*6 on the irinotecan label, which states that the *6 allele is uncommon in Black or African American and White people (see the medicines section). In a Chinese study of 117 people whose Gilbert syndrome was confirmed by gene testing, the most common disease-linked variants were the A(TA)7TAA promoter insertion and the p.Gly71Arg change; seven new variants were also found, and the authors described the overall pattern as similar to other Asian populations (Gu 2022).

A third variant, UGT1A1*60 (written c.-3279T>G), sits further upstream in the gene. A 2026 study from Nepal describes it as reducing gene transcription by about 40 percent and as highly prevalent in Asian populations. Among 75 Nepali patients with isolated unconjugated hyperbilirubinemia, 66.7 percent carried the G version on both copies, 29.3 percent on one copy and 4 percent on neither (Ghimire 2026).

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How Common It Is, Population by Population

Estimates vary with the population studied and with how Gilbert syndrome is defined — by a blood bilirubin cutoff, by a genotype, or by a doctor's recorded diagnosis.

• Overall range. A clinical reference review puts the prevalence at 2 to 20 percent depending on ethnicity (Grant 2024). An oncology pharmacy review describes it as affecting about 10 percent of the population (Ha 2017), and a 2025 Chinese drug-interaction review gives 5 to 10 percent (Dacheng 2025).
• United Kingdom. Among 463,060 genotyped UK Biobank participants, 46,189 (about 10 percent) carried two copies of a marker (rs887829-T) that defines the Gilbert genotype. Only 1,701 of them — 3 percent — had a coded diagnosis of Gilbert syndrome in their health records (Hamilton 2023).
• Women may be undercounted. A French analysis of 138,125 apparently healthy middle-aged UK Biobank participants argued that the standard single cutoff of 1 mg/dL (17 µmol/L) misses many women. Using cutoffs set separately by sex and age, 10 percent of women (7,741 of 76,809) were classed as having Gilbert syndrome, against 3.7 percent with the single cutoff (Poynard 2023).
• Egypt. In an Egyptian adult study, 101 people met the criteria for Gilbert syndrome, a prevalence of about 8 percent; the homozygous A(TA)7TAA promoter was the most frequent genotype (Kamal 2019).
• Chile. In 991 Chileans with normal liver tests from a national health survey, 2.6 percent had Gilbert-range bilirubin (4.5 percent of men, 0.5 percent of women), although 11.7 percent carried the *28 promoter on both copies — a share similar to Europeans (Méndez 2013).
• By ancestry, for the *28 genotype. The irinotecan label states that about 20 percent of Black or African American, 10 percent of White and 2 percent of East Asian individuals carry *28 on both copies, and about 2 to 6 percent of East Asian individuals carry *6 on both copies. In a large HIV treatment trial, *28 on both copies was found in 8 percent of white, 24 percent of Black and 18 percent of Hispanic participants (Ribaudo 2013). A US study of 138 healthy volunteers found the double-*28 genotype in 13 percent of people of European descent and 5 percent of people of Asian descent (Liu 2007).

The gap between genotype and diagnosis is the consistent thread: far more people carry the slow variant than ever receive the label, and a sizeable share of carriers never show raised bilirubin at all (Bosma 1995; Hamilton 2023; Méndez 2013).

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Symptoms, and Their Frequent Absence

Many people with Gilbert syndrome never know they have it; the UK Biobank figure above, where only 3 percent of genotype carriers had a recorded diagnosis, shows how often it passes unnoticed (Hamilton 2023). The clinical reference review states that most people with Gilbert syndrome have no symptoms of liver disease but may have symptoms related to triggers (Grant 2024). In its typical form, according to the pediatric review, the raised bilirubin is first noticed as mild jaundice that comes and goes during adolescence (Fretzayas 2012).

The Egyptian study followed its participants over time and recorded more than yellowing. In 47 people, jaundice that came and went was the only sign. In 54 of the 101, the jaundice came with abdominal pain, indigestion or loss of appetite. During jaundice episodes, participants scored worse than controls on quality-of-life measures of vitality, emotional role, social functioning, worry and general health. Vitamin D (25-hydroxyvitamin D3) levels also differed significantly between people with Gilbert syndrome and controls (Kamal 2019). These are associations found in one population; the study does not show that the bilirubin itself causes the abdominal symptoms.

The Nepali study, by contrast, highlights what is absent: blood-count measurements were within normal ranges for every genotype, and ultrasound found no enlargement of the liver or spleen. Average bilirubin rose with the number of *60 copies — 4.3 mg/dL with two copies, 3.2 mg/dL with one and 2.4 mg/dL with none — and 69.3 percent of the patients were male (Ghimire 2026).

Gilbert syndrome can add to other causes of raised bilirubin. The pediatric review states that, combined with breastfeeding, glucose-6-phosphate dehydrogenase deficiency, thalassemia, hereditary spherocytosis or cystic fibrosis, it may contribute to severe hyperbilirubinemia and/or gallstones (Fretzayas 2012). The newborn side of this is covered on the Neonatal Jaundice page.

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What Pushes Bilirubin Higher

Because the enzyme works at a reduced rate, anything that adds to the bilirubin load or slows the liver further can tip levels high enough to see. Sources name these triggers:

• Fasting and very low calorie intake. The Egyptian study listed fasting for more than 12 hours and low-calorie weight-loss plans as risk factors for visible jaundice (Kamal 2019); the clinical reference review also lists fasting (Grant 2024).
• Illness. Systemic infections in the Egyptian study (Kamal 2019); "intercurrent illness" in the reference review (Grant 2024).
• Hard physical exertion. "Intensive physical effort" was a listed risk factor in the Egyptian study (Kamal 2019).
• Menstruation and dehydration. Both are named as triggers in the clinical reference review (Grant 2024).
• Pregnancy, surgery and anesthesia. In the Egyptian study, pregnancy was linked to a significant rise in unconjugated bilirubin that persisted through the pregnancy, and general anesthesia was a listed risk factor (Kamal 2019).
• Some medicines. In the same study, 12 people with Gilbert syndrome developed significant unconjugated hyperbilirubinemia during direct-acting antiviral treatment for hepatitis C, even though the treatment cleared the virus (Kamal 2019). Medicines that block UGT1A1, such as atazanavir, are covered below.

The yellowing these triggers produce passes once the trigger passes. The bilirubin animation includes a Gilbert scenario that shows the same slower conjugation step.

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How It Is Identified

Reviews describe Gilbert syndrome mainly as a diagnosis made by ruling other things out. The clinical reference review states that it must be told apart from the other causes of a high unconjugated bilirubin — problems with bilirubin uptake, conjugation and overproduction, including the many forms of hemolysis (red-cell destruction) such as inherited enzyme deficiencies, hemoglobin disorders, red-cell membrane defects, infections, medicines, toxins and autoimmune hemolysis. It also notes that in liver and bile-duct disorders the share of conjugated bilirubin rises, whereas normally about 95 percent of the bilirubin in blood is unconjugated (Grant 2024).

The usual pattern described across the sources is:

• A raised bilirubin that is mostly unconjugated (indirect). Many studies use a total bilirubin of 1 mg/dL (17 µmol/L) or more as the threshold (Poynard 2023); the Chilean study used 1.4 to 5 mg/dL (Méndez 2013).
• Normal liver tests. The Chilean study counted only people with normal liver enzymes — alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) (Méndez 2013), and the oncology review notes that in Gilbert syndrome hepatic function remains normal despite the raised bilirubin (Ha 2017). These and the other routine blood chemistry values appear on the Comprehensive Metabolic Panel page.
• No sign of hemolysis. In the Nepali study, patients with hemolysis or liver and bile-duct disease were excluded, and blood-count measurements were normal (Ghimire 2026).
• Gene testing when the picture is unclear. The pediatric review states that molecular genetic tests can be done when there is a diagnostic problem (Fretzayas 2012). Reviews describe diagnosis by clinical presentation, blood chemistry and genotyping, and state that a precise diagnosis avoids unnecessary invasive procedures for suspected more serious liver disease (Strassburg 2010) — liver biopsy is the example given in a 2012 review of UGT1A1 genotyping (Gil 2012). The Chinese study used sequencing of the whole UGT1A1 gene to confirm 117 cases (Gu 2022).

The French UK Biobank analysis adds a caution about cutoffs: because bilirubin varies with the *28 genotype, sex and age, a single cutoff for everyone underestimates Gilbert syndrome in women (Poynard 2023).

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Medicines Affected by Slower UGT1A1

The same enzyme that clears bilirubin also clears some medicines. An oncology pharmacy review notes that a slower UGT1A1 can reduce the ability to clear certain drugs, that severe or even life-threatening toxicity can follow with some cancer drugs, and that many product labels set dose changes for "liver function" using serum bilirubin as the marker — even though in Gilbert syndrome the liver works normally and the bilirubin is high for a different reason. It found scant literature to guide dose adjustment (Ha 2017). A 2025 review adds that some drugs raise or lower UGT1A1 activity and so move bilirubin up or down (Dacheng 2025).

Irinotecan

Irinotecan, a chemotherapy drug used in colorectal (bowel) cancer among others, is turned in the body into an active compound called SN-38, which UGT1A1 then inactivates. The United States Food and Drug Administration-approved label for irinotecan hydrochloride injection states that people who carry *28 or *6 on both copies, or one of each (*28/*28, *6/*6, *6/*28), are "UGT1A1 poor metabolizers," have higher exposure to SN-38, and are at increased risk for severe or life-threatening neutropenia (a dangerous fall in infection-fighting white blood cells). People with one copy of either allele are described as intermediate metabolizers who may also have an increased risk. The label states that the risk of severe diarrhea also appears greater in *28 and *6 carriers, particularly homozygous patients and at irinotecan doses above 125 mg/m². Its dosing section states that a reduction in the starting dose by at least one level is to be considered for people known to be homozygous or compound heterozygous, and that UGT1A1 genotype testing for *28 and *6 is to be considered. The label is available on DailyMed.

A 2024 meta-analysis of 30 studies and 4,471 colorectal cancer patients found that *28 was associated with more diarrhea and neutropenia; in the recessive model (two copies) the odds ratio was 3.24 for diarrhea and 4.10 for neutropenia, with consistent results in Asian and non-Asian patients. *6 was associated with neutropenia across all genetic models and with diarrhea in the recessive model (Nguyen 2024).

Sacituzumab govitecan

Sacituzumab govitecan is an antibody-drug conjugate that delivers SN-38 directly to tumours, and its toxicity closely resembles irinotecan's. A 2026 meta-analysis of four clinical trials with 999 genotyped patients found that people with *28 on both copies had about seven times the odds of severe (grade 3 or higher) toxicities combined (odds ratio 7.03), and were more likely to need dose reductions and treatment interruptions (Dello Russo 2026).

Atazanavir

Atazanavir, an HIV protease inhibitor, blocks UGT1A1. Its label states that most patients taking it experience asymptomatic rises in indirect (unconjugated) bilirubin related to this inhibition, that the rise reverses when the drug is stopped, that rises in liver transaminases occurring alongside are to be evaluated for other causes, and that no long-term safety data exist for bilirubin persistently above 5 times the upper limit of normal. The label also states that atazanavir may interfere with irinotecan's breakdown and increase irinotecan toxicity. A 2019 meta-analysis of six studies found that HIV patients on atazanavir with *28 on both copies had about 10 times the odds of hyperbilirubinemia compared with those with no copies (odds ratio 10.07) (Du 2019). In a large randomised trial, the double-*28 genotype was linked to higher bilirubin, but to more stopping of atazanavir only among Hispanic participants, not white or Black participants; even among Hispanic participants, only 32 percent of those with the genotype stopped the drug (Ribaudo 2013).

The Liver Phase 1 and Phase 2 page places UGT1A1 among the other drug-clearing enzymes, and the Pharmacogenomics page covers gene testing before prescribing more broadly.

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Raised Bilirubin and the Heart: Observational Findings

Bilirubin acts as an antioxidant in laboratory studies, and a long line of research has asked whether people whose bilirubin runs a little high are protected from heart disease. A 2008 review summarised retrospective and prospective studies, and a meta-analysis, showing that serum bilirubin is inversely related to cardiovascular disease, and discussed prospective studies in people with Gilbert syndrome and the *28 allele (Schwertner 2008). All the studies in this section are observational: they show associations, not that bilirubin causes the difference.

• Czech study, 2002. Among 50 people with Gilbert syndrome over age 40, ischemic heart disease was found in 2 percent, against 12.1 percent in the comparable general population. Bilirubin, total antioxidant capacity and high-density lipoprotein (HDL) cholesterol were all higher in the Gilbert group (Vítek 2002).
• Framingham Heart Study, 2006. In 1,780 people followed for 24 years, those with *28 on both copies (11 percent of the population) had average bilirubin of 1.14 mg/dL versus 0.69 mg/dL in the rest, and about one third the risk of cardiovascular disease (hazard ratio 0.36) and coronary heart disease (hazard ratio 0.30) (Lin 2006).
• UK statin cohort, 2012. In 130,052 people whose bilirubin was measured before they started a statin, the relationship was L-shaped: compared with a bilirubin of 10 µmol/L (0.6 mg/dL), a level of 5 µmol/L (0.3 mg/dL) was linked to an 18 percent higher risk of any cardiovascular event, 34 percent higher risk of heart attack and 33 percent higher risk of death from any cause (Horsfall 2012). This finding concerns low bilirubin, not Gilbert-range levels specifically.
• Systematic review, 2026. A review of eight articles concluded that cardiovascular risk was lower in people with Gilbert syndrome than in unaffected people, and listed proposed explanations including lower lipids, less inflammation, higher antioxidant capacity, lower body mass index and lower triglycerides (Churchill 2026).

The genetic test of the idea. Mendelian randomisation uses a gene variant as a natural experiment: if bilirubin itself protects the heart, people born with the Gilbert genotype should show the same benefit. In UK Biobank, higher measured bilirubin had strong inverse associations with heart attack, chronic obstructive pulmonary disease, cholesterol measures and overall health, but these associations were not found in people with the Gilbert genotype. The authors concluded that bilirubin has no likely causal role in protection from cardiovascular disease, chronic obstructive pulmonary disease or other key outcomes (Hamilton 2023). The French UK Biobank analysis likewise found that, after adjustment and Mendelian randomisation, differences in illnesses and survival between people with Gilbert-range and normal bilirubin were no longer significant, apart from gallstones in men (Poynard 2023). The observational associations and the genetic results therefore point in different directions, and the question is not settled.

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Gallstones, Lungs, Athletes and Other Associations

• Gallstones. Genetically higher bilirubin was associated with biliary and liver conditions in UK Biobank, including gallstones (odds ratio 1.16) (Hamilton 2023). In the French analysis, gallstones were the one illness that stayed significantly more common — in men with Gilbert-range bilirubin (odds ratio 1.50) — after adjustment and Mendelian randomisation (Poynard 2023). The pediatric review also lists gallstones as a possible result when Gilbert syndrome combines with red-cell disorders (Fretzayas 2012).
• Pityriasis rosea. UK Biobank found a new association between genetically predicted bilirubin and this skin rash (odds ratio 1.47) (Hamilton 2023).
• Lungs and overall death rate. In 504,206 UK adults with normal-range bilirubin and no liver or hemolytic disease, each 0.1 mg/dL higher bilirubin was associated with an 8 percent lower rate of lung cancer in men and 11 percent in women, a 6 percent lower rate of chronic obstructive pulmonary disease in men and a 3 percent lower death rate in men, with similar results in women (Horsfall 2011). The later genetic analysis did not support a causal role for bilirubin in chronic obstructive pulmonary disease (Hamilton 2023).
• Elite athletes. Among 536 Czech elite athletes, 22 percent had Gilbert-range bilirubin compared with 9.6 percent of the general Czech population, with a tendency to more *28 genotypes. The authors suggested mild bilirubin elevation might predispose to better sports performance (Woronyczová 2022). This was a cross-sectional comparison; it cannot show which came first, and hard exertion itself is listed as a trigger for raised bilirubin (Kamal 2019).

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How It Differs From Crigler-Najjar Syndrome

Crigler-Najjar syndrome comes from changes in the same UGT1A1 gene, and reviews describe the two as a spectrum: Gilbert syndrome is the mildest form, Crigler-Najjar type II is intermediate and Crigler-Najjar type I is the most severe (Strassburg 2010; Jesus Sá 2026). The differences in scale are large:

• How much enzyme is left. Gilbert syndrome leaves about 30 percent of normal glucuronidating activity (Bosma 1995). In the Japanese laboratory models, the Crigler-Najjar type II combination (G71R plus Y486D on both copies) left 6.2 percent (Yamamoto 1998). In type I the enzyme is completely deficient (Dhawan 2020).
• How rare it is. Crigler-Najjar syndrome has an estimated incidence of 0.6 to 1.0 per million live births (Ebrahimi 2018), against the several percent of the population with Gilbert syndrome.
• What happens. In type I, unconjugated bilirubin rises by 3 to 6 mg/dL per day in the newborn period and reaches levels dangerous to the brain between 5 and 14 days of age, with a risk of irreversible brain injury (kernicterus). Phototherapy is the mainstay of treatment, bilirubin worsens with age despite it, and liver transplantation is the only definitive therapy (Dhawan 2020). Gilbert syndrome, in contrast, needs no treatment (Grant 2024).
• How subtypes are told apart. Crigler-Najjar subtypes are usually distinguished by clinical criteria such as response to phenobarbital, together with molecular findings (Ebrahimi 2018).

The boundary can blur. In a family with a history of Crigler-Najjar type II, only the carriers whose other gene copy had the longer *28 promoter showed the mild raised bilirubin typical of Gilbert syndrome (Bosma 1995). A 2026 case report describes a newborn with one Crigler-Najjar type II variant and one *28 promoter whose bilirubin needed several courses of phototherapy early on and then fell to normal by 11 months, with normal growth and development (Jesus Sá 2026).

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What Is Not Known

• Why some carriers show it and others do not. The original 1995 study concluded the *28 promoter is necessary but not sufficient, and the Japanese models found single-copy G71R activity "somewhat high" for the syndrome, suggesting additional factors (Bosma 1995; Yamamoto 1998). Those additional factors are not identified in these sources.
• Whether bilirubin protects the heart. Observational studies and a 2026 review report lower cardiovascular disease, but the genetic analyses found no likely causal role (Churchill 2026; Hamilton 2023; Poynard 2023).
• The cause of the non-jaundice symptoms. The abdominal symptoms, quality-of-life changes and lower vitamin D in the Egyptian study are associations from a single population (Kamal 2019).
• How triggers work in detail. Menstruation and dehydration are named as triggers in a reference review, but the sources read for this page give no measured size of the effect (Grant 2024).
• Drug dosing beyond irinotecan. For most cancer drugs, the oncology review found scant literature to guide dose adjustment in Gilbert syndrome (Ha 2017), and the atazanavir label states there are no long-term safety data for very high persistent bilirubin.
• Diagnostic cutoffs. The standard single bilirubin threshold appears to underestimate Gilbert syndrome in women, and sex- and age-specific ranges have been proposed (Poynard 2023).

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Key Research Papers

1. Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med. 1995;333(18):1171-5. PubMed PMID: 7565971
2. Kamal S, Abdelhakam S, Ghoraba D, Massoud Y, Aziz KA, Hassan H, et al. The frequency, clinical course, and health related quality of life in adults with Gilbert's syndrome: a longitudinal study. BMC Gastroenterol. 2019;19(1):22. PubMed PMID: 30717703
3. Grant LM, Faust TW, Thoguluva Chandrasekar V, John S. Gilbert Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024. PubMed PMID: 29262099
4. Fretzayas A, Moustaki M, Liapi O, Karpathios T. Gilbert syndrome. Eur J Pediatr. 2012;171(1):11-5. PubMed PMID: 22160004
5. Strassburg CP. Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome). Best Pract Res Clin Gastroenterol. 2010;24(5):555-71. PubMed PMID: 20955959
6. Gil J, Sąsiadek MM. Gilbert syndrome: the UGT1A1*28 promoter polymorphism as a biomarker of multifactorial diseases and drug metabolism. Biomark Med. 2012;6(2):223-30. PubMed PMID: 22448797
7. Yamamoto K, Sato H, Fujiyama Y, Doida Y, Bamba T. Contribution of two missense mutations (G71R and Y486D) of the bilirubin UDP glycosyltransferase (UGT1A1) gene to phenotypes of Gilbert's syndrome and Crigler-Najjar syndrome type II. Biochim Biophys Acta. 1998;1406(3):267-73. PubMed PMID: 9630669
8. Gu L, Han Y, Zhang D, Gong Q, Zhang X. Genetic testing of UGT1A1 in the diagnosis of Gilbert syndrome: The discovery of seven novel variants in the Chinese population. Mol Genet Genomic Med. 2022;10(7):e1958. PubMed PMID: 35426266
9. Ghimire PG, Ghimire P, Pande R. Genetic, clinical, and biochemical profiling of Gilbert syndrome in a Nepali cohort: High prevalence of the UGT1A1 c.-3279T>G polymorphism and correlation with hematological parameters. PLoS One. 2026;21(4):e0347128. PubMed PMID: 41973709
10. Hamilton FW, Abeysekera K, Hamilton W, Timpson NJ. Effect of bilirubin and Gilbert syndrome on health: cohort analysis of observational, genetic, and Mendelian randomisation associations. BMJ Med. 2023;2(1):e000467. PubMed PMID: 37456363
11. Poynard T, Deckmyn O, Peta V, Sakka M, Lebray P, Moussalli J, et al. Clinical and genetic definition of serum bilirubin levels for the diagnosis of Gilbert syndrome and hypobilirubinemia. Hepatol Commun. 2023;7(10):e0245. PubMed PMID: 37738404
12. Méndez L, Lagoa M, Quiroga T, Margozzini P, Azócar L, Molina HR, et al. [Prevalence of Gilbert syndrome and its genetic determinants in Chile]. Rev Med Chil. 2013;141(10):1266-74. PubMed PMID: 24522354
13. Liu JY, Qu K, Sferruzza AD, Bender RA. Distribution of the UGT1A1*28 polymorphism in Caucasian and Asian populations in the US: a genomic analysis of 138 healthy individuals. Anticancer Drugs. 2007;18(6):693-6. PubMed PMID: 17762398
14. Ha VH, Jupp J, Tsang RY. Oncology Drug Dosing in Gilbert Syndrome Associated with UGT1A1: A Summary of the Literature. Pharmacotherapy. 2017;37(8):956-972. PubMed PMID: 28494109
15. Dacheng DC, Liang C, Zheng SJ. [Interactions between common drug metabolism and precautions for drug usage in Gilbert syndrome]. Zhonghua Gan Zang Bing Za Zhi. 2025;33(3):293-299. PubMed PMID: 40274556
16. Nguyen CTT, Nguyen TMT, Phung TH. Meta-analysis revisiting the influence of UGT1A1*28 and UGT1A1*6 on irinotecan safety in colorectal cancer patients. Pharmacogenomics. 2024;25(10-11):469-477. PubMed PMID: 39171626
17. Dello Russo C, Asiimwe IG, Pushpakom S, Palmieri C, Pirmohamed M. UGT1A1 and Sacituzumab Govitecan Toxicity: A Systematic Review and Meta-Analysis. Clin Pharmacol Ther. 2026;119(1):63-73. PubMed PMID: 40936312
18. Du P, Wang A, Ma Y, Li X. Association between the UGT1A1*28 allele and hyperbilirubinemia in HIV-positive patients receiving atazanavir: a meta-analysis. Biosci Rep. 2019;39(5):BSR20182105. PubMed PMID: 30962262
19. Ribaudo HJ, Daar ES, Tierney C, Morse GD, Mollan K, Sax PE, et al. Impact of UGT1A1 Gilbert variant on discontinuation of ritonavir-boosted atazanavir in AIDS Clinical Trials Group Study A5202. J Infect Dis. 2013;207(3):420-5. PubMed PMID: 23148286
20. Schwertner HA, Vítek L. Gilbert syndrome, UGT1A1*28 allele, and cardiovascular disease risk: possible protective effects and therapeutic applications of bilirubin. Atherosclerosis. 2008;198(1):1-11. PubMed PMID: 18343383
21. Vítek L, Jirsa M, Brodanová M, Kalab M, Marecek Z, Danzig V, et al. Gilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels. Atherosclerosis. 2002;160(2):449-56. PubMed PMID: 11849670
22. Lin JP, O'Donnell CJ, Schwaiger JP, Cupples LA, Lingenhel A, Hunt SC, et al. Association between the UGT1A1*28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart Study. Circulation. 2006;114(14):1476-81. PubMed PMID: 17000907
23. Horsfall LJ, Nazareth I, Petersen I. Cardiovascular events as a function of serum bilirubin levels in a large, statin-treated cohort. Circulation. 2012;126(22):2556-64. PubMed PMID: 23110860
24. Churchill N, Barry L, Nianogo R. Effects of Gilbert syndrome on cardiovascular disease risk reduction: a systematic review. Egypt Heart J. 2026;78(1):25. PubMed PMID: 42008064
25. Horsfall LJ, Rait G, Walters K, Swallow DM, Pereira SP, Nazareth I, et al. Serum bilirubin and risk of respiratory disease and death. JAMA. 2011;305(7):691-7. PubMed PMID: 21325185
26. Woronyczová J, Nováková M, Leníček M, Bátovský M, Bolek E, Cífková R, et al. Serum Bilirubin Concentrations and the Prevalence of Gilbert Syndrome in Elite Athletes. Sports Med Open. 2022;8(1):84. PubMed PMID: 35759151
27. Dhawan A, Lawlor MW, Mazariegos GV, McKiernan P, Squires JE, Strauss KA, et al. Disease burden of Crigler-Najjar syndrome: Systematic review and future perspectives. J Gastroenterol Hepatol. 2020;35(4):530-543. PubMed PMID: 31495946
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29. Jesus Sá C, Vilar Queirós R, Pessoa T, Santos S, Castilho S. Between Crigler-Najjar Syndrome Type II and Gilbert Syndrome: Expanding the Spectrum of Uridine Diphosphate Glucuronosyltransferase 1A1 (UGT1A1)-Related Hyperbilirubinemia. Cureus. 2026;18(1):e100926. PubMed PMID: 41658774

PubMed Topic Searches

1. PubMed: Gilbert syndrome and UGT1A1
2. PubMed: Gilbert syndrome prevalence
3. PubMed: UGT1A1*28 and irinotecan toxicity
4. PubMed: bilirubin, cardiovascular disease and Mendelian randomisation
5. PubMed: Crigler-Najjar and Gilbert syndromes

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Connections

• Hematology — the blood disorders section
• Jaundice — all the causes of yellow skin and eyes
• Bilirubin and Jaundice Animation — includes a Gilbert scenario
• Liver Phase 1 and Phase 2 — UGT1A1 among the drug-clearing enzymes
• Neonatal Jaundice — where Gilbert variants add to newborn bilirubin
• G6PD Deficiency — a red-cell disorder that can combine with it
• Hereditary Spherocytosis — another red-cell disorder named in reviews
• Pharmacogenomics — gene testing before prescribing
• Comprehensive Metabolic Panel — where bilirubin and liver enzymes are reported

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