UGT1A6 polymorphism and plasma bilirubin are associated with antioxidant status in male smokers

This study was conducted to investigate the relationship between plasma total bilirubin level and antioxidant status and to assess the role of UDP‐glucuronosyltransferase (UGT) 1A6 genetic polymorphism, which affects glucuronidation of bilirubin and thus may induce an altered level of bilirubin, in the antioxidant status in male smokers. Plasma antioxidant parameters[TRAP, lipid‐soluble vitamins(Retinol, γ‐, α‐tocopherol, α‐, β‐carotene, and coenzyme Q10), lipid peroxidation, erythrocyte antioxidant enzyme activities(SOD, CAT, and GPx), leukocytes DNA damage], and genetic polymorphisms for UGT1A6 were assessed in 162 male smokers with no evidence of disease and no major risk factors for liver disease. When the subjects were classified into the four groups by quartiles of bilirubin levels, significant differences in TRAP, retinol, γ‐, α‐tocopherol, α‐carotene and coenzyme Q10, activities of erythrocytes antioxidant enzymes(SOD and CAT), and leukocytes DNA damage were found among the groups. In the simple linear regression, the higher level of plasma total bilirubin was associated with the significantly increased TRAP(r 2 =0.044, p<0.001) and α‐tocopherol(r 2 =0.092, p<0.001). Additionally, the levels of plasma total bilirubin, TRAP, retinol, γ‐, α‐tocopherol, and coenzyme Q10, activities of SOD and CAT, and leukocyte DNA damage depend on variations of UGT1A6 genotypes(homo+hetero), when AST and ALT were adjusted. These results suggested that the increased plasma total bilirubin within normal range may be accompanied with enhanced physiological antioxidant status in healthy male smokers. Also, the presence of variant UGT1A6 genotypes seem to be associated with altered antioxidant status assumedly mediated by plasma total bilirubin concentration.