Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery disease

Arno Lingenhel, Barbara Kollerits, Johannes P. Schwaiger, Steven Hunt, Richard Gress, Paul N. Hopkins, Veit Schoenborn, Iris M. Heid, Florian Kronenberg

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Abstract

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 × 10-10; and 0.42 ± 0.29 vs. 0.55 ± 0.23 mg/dl, p = 1.9 × 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 × 10-26 and p = 3.4 × 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 × 10-6 for men and 0.77 (0.68-0.87), p = 3.2 × 10-5 for women, respectively for each 0.1 mg/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.

Original languageEnglish
Pages (from-to)1102-1107
Number of pages6
JournalExperimental Gerontology
Volume43
Issue number12
DOIs
Publication statusPublished - Dec 2008
Externally publishedYes

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Keywords

  • Association study
  • Bilirubin
  • Coronary artery disease
  • Polymorphism
  • UGT1A1

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

Lingenhel, A., Kollerits, B., Schwaiger, J. P., Hunt, S., Gress, R., Hopkins, P. N., Schoenborn, V., Heid, I. M., & Kronenberg, F. (2008). Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery disease. Experimental Gerontology, 43(12), 1102-1107. https://doi.org/10.1016/j.exger.2008.08.047