UGT1A1 promoter genotype is not strongly associated with severity of coronary artery disease.

Atherosclerosis is a leading cause of morbidity and mortality. Oxidative stress is thought to play a role in its pathogenesis. Bilirubin is an endogenous antioxidant that is mildly elevated in people with Gilbert syndrome. Homozygosity for a A(TA)7TAA variant of the UDP-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) promoter is necessary for expression of the Gilbert phenotype. We studied the relationship between coronary artery disease (CAD) and the Gilbert genotype. Decedents who underwent autopsy were categorized into none/mild, moderate, and severe CAD groups based on autopsy findings. Known CAD risk factors were evaluated for each decedent in the severe CAD group (n=35), and for an age, race, and sex-matched control group with none/mild CAD (n=45). Formalin-fixed paraffin-embedded (FFPE) tissue was tested for UGT1A1 promoter variants by polymerase chain reaction and capillary electrophoresis. To our knowledge, this is the first study to successfully apply UGT1A1 promoter genotyping to formalin-fixed paraffin-embedded tissue, which may facilitate more thorough examination of clinicopathologic correlations. The frequency of the Gilbert genotype was compared between the none/mild cohort and the severe cohort. UGT1A1 promoter genotype data were obtained for 76/80 cases. The overall frequency of the Gilbert genotype compared well with previously reported frequencies at 16%, with a frequency of 16% in the none/mild CAD group and 15% in the severe CAD group. These findings suggest that UGT1A1 promoter genotype is not a major factor contributing to risk of CAD.