Serum bilirubin and genes controlling bilirubin concentrations as biomarkers for cardiovascular disease. Clin Chem

BACKGROUND: Serum bilirubin has been consistently shown to be inversely related to cardiovascular disease (CVD). Recent studies showed serum bilirubin to be associated with CVD-related factors such as diabetes, metabolic syndrome, and body mass index. Although the association of serum bilirubin with CVD has been found in both retrospective and prospective studies, less information is available on the role of genes that control bilirubin concentrations and their association with CVD. CONTENT: In this review, we provide detailed infor-mation on the identity of the major genes that con-trol bilirubin concentrations and their association with serum bilirubin concentrations and CVD risk. We also update the results of the major studies that have been performed on the association between se-rum bilirubin, CVD, and CVD-related diseases such as diabetes or metabolic syndrome. Studies consis-tently indicate that bilirubin concentrations are in-versely associated with different types of CVD and CVD-related diseases. A conditional linkage study indicates that UGT1A1 is the major gene controlling serum bilirubin concentrations, and this finding has been confirmed in recent genomewide association studies. Studies also indicate that individuals ho-mozygous for UGT1A1*28 have a significantly lower risk of developing CVD than carriers of the wild-type alleles. SUMMARY: Serum bilirubin has a protective effect on CVD and CVD-related diseases, and UGT1A1 is the major gene controlling serum bilirubin concentra-tions. Pharmacologic, nonpharmacologic, or genetic interventions that increase serum bilirubin concentra-tions could providemore direct evidence on the role of bilirubin in CVD prevention