Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Association between bilirubin and cardiovascular disease risk factors: using Mendelian randomization to assess causal inference.

Patrick F McArdle; Brian W Whitcomb; Keith Tanner; Braxton D Mitchell; Alan R Shuldiner; Afshin Parsa (Profiled Authors: Patrick McArdle; Braxton D Mitchell Jr.; Afshin Parsa; Alan R Shuldiner)

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, 660 West Redwood Street, Rm, 492, Baltimore, MD 21201, USA. pmcardle@medicine.umaryland.edu
BMC cardiovascular disorders 2012;12():16.

BACKGROUND: Elevated serum bilirubin has been associated with reduced risk of cardiovascular disease (CVD). However, serum bilirubin is also related with several potential confounders related to CVD, such as obesity. Mendelian randomization has been proposed as a method to address challenges to validity from confounding and reverse causality. It utilizes genotype to estimate causal relationships between a gene product and physiological outcomes. In this report, we demonstrate its use in assessing direct causal relations between serum bilirubin levels and CVD risk factors, including obesity, cholesterol, measures of vascular function and blood pressure. METHODS: Study subjects included 868 asymptomatic individuals. Study subjects were genotyped at the UGT1A1*28 locus, which is strongly associated with bilirubin levels. RESULTS: Serum bilirubin levels were inversely associated with levels of several cardiovascular disease risk factors, including body mass index (p=0.003), LDL (p=0.0005) and total cholesterol (p=0.0002). In contrast, UGT1A1*28 genotype, a known cause of elevated bilirubin levels, was not significantly associated with any of these traditional CVD risk factors. We did observe an association between genotype and brachial artery diameter (p=0.003) and cold pressor reactivity (p=0.01). CONCLUSIONS: Our findings imply that the observed association of serum bilirubin levels with body mass index and cholesterol are likely due to confounding and suggest that previously established CVD benefits of increased bilirubin may in part be mediated by the early regulation of vascular structure and reactivity.

3 Originating Grant

• 1.

  SHULDINER, ALAN R.

  Mid-Atlantic Nutrition Obesity Research Center

  15 September 2005 - 31 August 2015

  NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

• 2.

  Shuldiner, Alan R

  Genome-wide Search for CVD Gene-Environment Interactions

  30 September 2002 - 31 May 2009

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

• 3.

  Reece, E Albert

  General Clinical Research Center

  1 March 2002 - 30 June 2010

  NATIONAL CENTER FOR RESEARCH RESOURCES

Scientific Context

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