An Investigation into Gilbert’s Syndrome: Understanding the Role of Unconjugated Bilirubin in Targeting Platelet and Haemostatic Mechanisms Associated with Thrombotic Risk Factors

Abstract

Gilbert’s syndrome (GS) is a common genetic condition associated with mildly elevated unconjugated bilirubin (UCB) concentrations and increased protection against development of cardiovascular disease (CVD). Mutation in the uridine diphosphate glucuronosyltransferase (UGT1A1) gene causing a reduction in UGT1A1 enzyme activity that is responsible for conjugation and elimination of UCB, is considered as the cause for GS. Numerous studies have shown that elevated levels of UCB are negatively associated with risk of developing CVD. While, several in vitro and in vivo trials have shown that UCB at physiological concentrations can improve endothelial function, lipid profile and reduce vascular inflammation, thereby imparting its cardiovascular protection. Cardiovascular disease is a major cause of death globally, an estimated 17.3 million CVD related deaths are reported annually by the World Health Organization (WHO), making it the largest cause of human mortality. Furthermore, several studies have predicted that these numbers would continue rising in the coming years, due to factors such as aging, life style choices and environmental changes.