Bilirubin is the end product of the breakdown of hemoglobin from aged red blood cells. Bilirubin levels in the blood are an important indicator of liver function.
Bilirubin levels
Bilirubin is formed after degradation of the heme group that is part of the hemoglobin protein found in red blood cells, and of other heme-containing proteins (such as cytochrome P450 enzymes, myoglobin and the enzyme catalase). It is formed in the macrophages of the spleen and bone marrow and in hepatic Kupffer cells, and released into the plasma.
As bilirubin is poorly soluble, much of it is bound to the protein albumin (known as free, unconjugated or indirect bilirubin) and when taken up by the liver it is conjugated with glucuronic acid and becomes more soluble. This form is known as conjugated or direct bilirubin. Finally, the conjugated form passes into the intestine through the bile where it is broken down by anaerobic bacteria into the pigment urobilinogen. Much of the urobilinogen is excreted with the feces and a smaller portion is reabsorbed in the intestine and eliminated in the urine.
Number of observed variants
13.5 million variants
Number of risk loci
268 loci
Genes analyzed
Bibliography
Barton AR, Sherman MA, et al. Whole-exome imputation within UK Biobank powers rare coding variant association and fine-mapping analyses. Nat Genet. 2021 Aug;53(8):1260-1269.
Fevery J. Bilirubin in clinical practice: a review. Liver Int. 2008 May;28(5):592-605.
Johnson AD, Kavousi M, Smith A, et al. Genome-wide association meta-analysis for total serum bilirubin levels. Hum Mol Genet. 2009 Jul 15;18(14):2700-10.
Vítek L, Tiribelli C. Bilirubin: The yellow hormone? J Hepatol. 2021 Dec;75(6):1485-1490.
