Gilbert syndrome (pronounced "zheel-bare") is the most common inherited metabolic condition in the United States, affecting about 5 to 10 percent of the population. Wikipedia It is caused by a deficiency of the liver enzyme that metabolizes bilirubin (a breakdown product of hemoglobin, the oxygen-carrying component of red blood cells).
Most people are unaware that they have Gilbert syndrome unless a blood test shows elevated liver enzymes or bilirubin levels, which can be caused by infection, dehydration, fasting, treatment with antibiotics or other drugs [PMID 15179405], or some other physiological stress. If the person has not previously been diagnosed with Gilbert syndrome, a doctor may do tests to rule out more serious types of liver problems, so patients who know they have the condition may be able to avoid a full medical work-up for minor elevations in blood tests.
Some people with Gilbert syndrome occasionally show symptoms such as jaundice, which ordinarily does not need treatment other than rest. It may also be the cause of some cases of newborn jaundice. [PMID 9784835] Some people with Gilbert syndrome are susceptible to paracetamol (Tylenol) toxicity. [PMID 10412886] There may also be beneficial effects: for example, moderately elevated bilirubin levels may lower the risk of cardiovascular disease. Wikipedia
The most common allele, UGT1A1*28 (rs34983651), represents 7 (rather than the wild-type 6) TA repeats in the promoter region, resulting in markedly reduced production of the enzyme UDP-glucuronosyltransferase 1. The same variant also confers markedly increased sensitivity to irinotecan toxicity, because of reduced inactivation and clearance of the drug's active metabolite.
Gilbert syndrome is recessive, so carriers of one risk allele are not affected by the condition (although they may still be at increased risk of irinotecan toxicity). Genes involved include:
Some SNPs that may contribute to Gilbert syndrome include:
- rs6742078 [PMID 21412181]
- rs28934877, also associated with Crigler-Najjar syndrome type II NCBI
- rs4148323, also associated with Crigler-Najjar syndrome type II [PMID 15179404]
- rs34815109 UGT1A1*28 [PMID 17909964]
- rs4124874 Linked to lower transcriptional activity of UGT1A1 [PMID 15378351]