Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery disease.
Low levels of the antioxidative serum bilirubin are associated with vascular aging and an increased risk for coronary artery disease (CAD). UGT1A1 is the major gene influencing bilirubin concentrations. Therefore, we investigated an association of bilirubin levels and two polymorphisms in the promoter of UGT1A1 (-53(TA-repeat) polymorphism and T-3279G) in 477 patients with premature, familial CAD and 619 age- and sex-matched controls. Bilirubin concentrations were significantly lower in cases than in controls (0.62+/-0.36 vs. 0.76+/-0.41 mg/dl for men, p=1.2 x 10(-10); and 0.42+/-0.29 vs. 0.55+/-0.23 mg/dl, p=1.9 x 10(-9) for women). Both polymorphisms showed a strong association with bilirubin levels with higher levels for homozygote carriers of the minor allele. These associations were most pronounced in male controls and patients (p=5.9 x 10(-26) and p=3.4 x 10(-16), respectively, for the -53(TA-repeat) polymorphism). Logistic regression analysis revealed low bilirubin levels but not the UGT1A1 polymorphisms to be significantly associated with CAD: OR (95% CI) 0.90 (0.86-0.94), p=2.6 x 10(-6) for men and 0.77 (0.68-0.87), p=3.2 x 10(-5) for women, respectively for each 0.1mg/dl increase of bilirubin. These results indicate that it is rather decreased bilirubin levels in general than the changes in the genetic variation of this gene that increase the risk for CAD.
Lingenhel
Arno
A
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstrasse 41, A-6020 Innsbruck, Austria.
Kollerits
Barbara
B
Schwaiger
Johannes P
JP
Hunt
Steven C
SC
Gress
Richard
R
Hopkins
Paul N
PN
Schoenborn
Veit
V
Heid
Iris M
IM
Kronenberg
Florian
F
D001663:Bilirubin / Q000378:metabolism*; D016022:Case-Control Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme
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