UGT1A1*28 Allele and Coronary Heart Disease: The Rotterdam Study (Technical Briefs‪)‬

Oxidative reactions, such as lipid oxidation and the formation of oxygen radicals, are involved in the pathophysiology of arteriosclerosis and coronary heart disease (CHD) (1). Bilirubin, the metabolic waste product of heme degradation, is an endogenous antioxidant and could thus have a protective effect against CHD (2). In vitro, conjugated and unconjugated bilirubin are scavengers of peroxyl radicals and are able to protect human LDL against peroxidation (3, 4). In vivo, increased serum bilirubin was shown to produce an enhanced antioxidant status of serum (5). In addition, an association between low serum bilirubin and the risk of CHD has been observed in several studies (6-8). A recent family heart study inferred the existence of a major gene for high bilirubin concentrations that may protect against CHD (9). A likely candidate gene responsible for high serum bilirubin is the gene encoding the hepatic enzyme bilirubin UDP-glucuronosyltransferase (UGT1A1). Glucuronidation is an essential step in the biliary excretion of bilirubin, and decreased UGT1A1 activity leads to increased serum concentrations of unconjugated bilirubin (10). A common etiology of decreased UGT1A1 activity is the insertion of a TA in the TATAA box in the promoter region of the UGT1A1 gene (11). Transcription of the UGT1A1 gene is fivefold lower in individuals with this allele, designated UGT1A1*28.