The UGT1A1∗28 gene variant predicts long-term mortality in patients undergoing coronary angiography

Abstract

Uridine diphosphate glycosyltransferases 1A1 (UGT1A1) plays an essential role in detoxification and excretion of several endogenous and exogenous compounds. A functional polymorphism in the promoter of the UGT1A1 gene (TA repeat insertion, UGT1A1∗28, rs3064744) has been associated with reduced UGT1A1 enzyme activity. The purpose of the present study was to investigate the role of UGT1A1 genotypes in mortality. UGT1A1 genotypes as well as baseline plasma bilirubin levels were analyzed in participants of the Ludwigshafen Risk and Cardiovascular Health study (n=3316). UGT1A1∗28 genotypes were determined on an ABI PRISM 3730 genetic analyzer. As expected, UGT1A1 genotypes were associated with baseline bilirubin levels (∗1/∗1 genotype: 9.1±4.6 μmol/L; ∗1/∗28 genotype: 10.8±5.3; ∗28/∗28: 16.9±9.2; p<0.001). During a median follow-up of 10.4 years, 995 subjects (30.0%) died. In a multivariate regression analysis adjusting for age, sex, smoking, type 2 diabetes, dyslipidemia, alanine aminotransferase (ALT) levels and bilirubin levels, the UGT1A1∗28 variant predicted lower overall mortality (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.78-0.95; p=0.003). Contrary to expected, higher baseline bilirubin levels predicted increased mortality (HR, 1.014; 95% CI, 1.002-1.025; p=0.019). The UGT1A1∗28 gene variant is associated with lower mortality rates. The protective effect of the UGT1A1∗28 variant likely includes mechanism other than bilirubin metabolism.