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

DOI: 10.1186/1471-2261-12-16

Keywords: Bilirubin, Mendelian randomization, Cardiovascular disease

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Abstract:

Study subjects included 868 asymptomatic individuals. Study subjects were genotyped at the UGT1A1*28 locus, which is strongly associated with bilirubin levels.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).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.Bilirubin is a metabolic byproduct of the breakdown of hemoglobin degradation which itself must be metabolized for appropriate excretion. High levels of bilirubin are associated with decreased risk of coronary heart disease (CHD) and cardiovascular disease (CVD) [1]. While the full spectrum by which bilirubin acts to protect against CVD is not fully understood, there has been evidence of protecting against oxidative stress by reducing reactive oxygen species and possibly having additional anti-atherogenetic properties [2,3]. Previous studies have reported associations of serum bilirubin levels to cardiovascular disease risk factors, including total cholesterol and blood pressure [4-6]. Serum bilirubin levels have also been associated with socioeconomic and behavioral CVD risk factors such as smoking and alcohol intake [7,8]. However, the nature of these associations is unclear, including the potential for residual confounding among serum bilirubin levels and the associated CVD risk factors due to factors measured poorly or not measured

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