Genetically elevated bilirubin and risk of ischaemic heart disease: three Mendelian randomization studies and a meta‐analysis. (20th August 2012)

• Record Type: Journal Article
• Authors: Stender, S.; Frikke‐Schmidt, R.; Nordestgaard, B. G.; Grande, P.; Tybjærg‐Hansen, A.
• Is Part Of: Journal of internal medicine. Volume 273:Number 1(2013:Jan.)
• Page Start: 59
• Page End: 68
• Publication Date: 2012-08-20
• Subjects: Internal medicine -- Periodicals; Medicine -- Periodicals; 616
• DOI: 10.1111/j.1365-2796.2012.02576.x
• Languages: English
• ISSNs: 0954-6820

Abstract

<abstract abstract-type="main" id="joim2576-abs-0001"> <title>Abstract</title> <sec id="joim2576-sec-0001" sec-type="section"> <title>Background</title> <p>Elevated plasma levels of bilirubin, an endogenous antioxidant, have been associated with reduced risk of ischaemic heart disease (IHD) and myocardial infarction (MI). Whether this is a causal relationship remains unclear.</p> </sec> <sec id="joim2576-sec-0002" sec-type="section"> <title>Objective</title> <p>We tested the hypothesis that elevated plasma bilirubin is causally related to decreased risk of IHD and MI.</p> </sec> <sec id="joim2576-sec-0003" sec-type="section"> <title>Design</title> <p>We used a Mendelian randomization approach and three independent studies from Copenhagen, Denmark. We measured bilirubin in 43 708 white individuals from the general population, and genotyped rs6742078 G>T in the uridine diphosphate glucuronosyltransferase 1A1 (<italic>UGT1A1</italic>) gene in 67 068 individuals, of whom 11 686 had IHD.</p> </sec> <sec id="joim2576-sec-0004" sec-type="section"> <title>Results</title> <p>Third versus first tertile of baseline bilirubin levels was associated with 134% increased bilirubin levels, with sex‐ and age‐adjusted hazard ratios (HRs) of 0.86 [95% confidence interval (CI), 0.76–0.98; <italic>P</italic> = 0.02] for IHD and 0.81 (95% CI, 0.66–0.99; <italic>P</italic> = 0.04) for MI, but with corresponding multifactorially adjusted HRs of 0.93 (95% CI, 0.82–1.06; <italic>P</italic> = 0.29) and 0.90 (95% CI, 0.73–1.12; <italic>P</italic> = 0.35). <italic>UGT1A1</italic> rs6742078 TT versus GG genotype was associated with 95% increased bilirubin levels (<italic>P </italic>< 0.001); TT versus GG genotype was associated with odds ratios (ORs) of 1.03 (95% CI, 0.96–1.11; <italic>P</italic> = 0.73) for IHD and 1.01 (95% CI, 0.92–1.12; <italic>P</italic> = 0.68) for MI. Finally, in a meta‐analysis of the present three studies and eight previous studies including a total of 14 711 cases and 60 324 controls, the random effects OR for ischaemic cardiovascular disease for genotypes with approximately 100% increased bilirubin levels versus reference genotypes was 1.01 (95% CI, 0.88–1.16).</p> </sec> <sec id="joim2576-sec-0005" sec-type="section"> <title>Conclusion</title> <p>These data suggest that plasma bilirubin is not causally associated with risk of IHD.</p> </sec> </abstract>