Plasma bilirubin and UGT1A1*28 are not protective factors against first-time myocardial infarction in a prospective, nested case-referent setting.
BACKGROUND
Bilirubin, an effective antioxidant, shows a large variation in levels between individuals and has been positively associated with reduced cardiovascular disease risk. A major reason for the variability is a common promoter polymorphism, UGT1A1*28, which reduces the transcription of the enzyme that conjugates bilirubin, UDP-glucuronosyltransferase 1A1. The aim of the study was to evaluate a possible protective effect of plasma bilirubin and the UGT1A1*28 polymorphism against myocardial infarction in a prospective case-referent setting.


RESULTS
Subjects (n=618) with a first-ever myocardial infarction (median event age, 60.5 years; median lag time, 3.5 years) and 1184 matched referents were studied. Plasma bilirubin was lower in cases versus referents. Despite a strong gene-dosage effect on bilirubin levels in both cases and referents, the UGT1A1*28 polymorphism did not influence the risk of myocardial infarction. Among multiple other variables, serum iron showed one of the strongest associations with bilirubin levels.


CONCLUSIONS
We found no evidence for a protective effect of the UGT1A1*28 polymorphism against myocardial infarction and consequently neither for bilirubin. The lower bilirubin levels in cases might be caused by decreased production, increased degradation, or increased elimination.
Ekblom
Kim
K
Clinical Chemistry, Department of Medical Biosciences, Umeå University, Umeå Sweden. kim.ekblom@medbio.umu.se
Marklund
Stefan L
SL
Jansson
Jan-Håkan
JH
Osterman
Pia
P
Hallmans
Göran
G
Weinehall
Lars
L
Hultdin
Johan
J
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001663:Bilirubin / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D019610:Cytoprotection / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000502:physiology; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000502:physiology; D011446:Prospective Studies; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme