A genome scan for loci influencing anti-atherogenic serum bilirubin levels

Florian Kronenberg, Hilary Coon, Alexader Gutin, Victor Abkevich, Mark E. Samuels, Dennis G. Ballinger, Paul N. Hopkins, Steven C. Hunt

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Epidemiological studies have shown an association of decreased serum bilirubin levels with coronary artery disease. Two segregation analyses in large pedigrees have suggested a major gene responsible for high bilirubin levels occurring in about 12% of the population. Based on a recessive model from a previous segregation analysis, we performed a genome scan using 587 markers genotyped in 862 individuals from 48 Utah pedigrees to detect loci linked to high bilirubin levels. As a complementary approach, non-parametric linkage (NPL) analysis was performed. These two methods identified four regions showing evidence for linkage. The first region is on chromosome 2q34-37 with multipoint LOD and NPL scores of 3.01 and 3.22, respectively, for marker D2S1363. This region contains a previously described gene, uridine cliphosphate glycosyltransferase 1, which has been associated with high bilirubin levels. A polymorphism in the promoter of this gene was recently shown to be responsible for Gilbert syndrome which is associated with mild hyperbilirubinemia. The other regions were found on chromosomes 9q21, 10q25-26, and 18q12 with maximum NPL scores of 2.39, 1.55, and 2.79, respectively. Furthermore, we investigated in these pedigrees the association between bilirubin levels and coronary artery disease. One-hundred and sixty-one male and 41 female subjects had already suffered a coronary artery disease event. Male patients showed significantly lower bilirubin concentrations than age-matched controls. This association, however, was not observed in females. These results provide evidence that loci influencing bilirubin variation exist on chromosomes 2q34-37, 9q21, 10q25-26, and 18q12 and confirms the association of low bilirubin levels with coronary artery disease in males.

Original languageEnglish
Pages (from-to)539-546
Number of pages8
JournalEuropean Journal of Human Genetics
Issue number9
Publication statusPublished - 1 Jan 2002



  • Antioxidants
  • Atherosclerosis
  • Bilirubin
  • Coronary artery disease
  • Genetics
  • Linkage analysis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Kronenberg, F., Coon, H., Gutin, A., Abkevich, V., Samuels, M. E., Ballinger, D. G., Hopkins, P. N., & Hunt, S. C. (2002). A genome scan for loci influencing anti-atherogenic serum bilirubin levels. European Journal of Human Genetics, 10(9), 539-546. https://doi.org/10.1038/sj.ejhg.5200842