Office of Biostatistics Research, Division of Cardiovascular Science, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Clin Chem. 2010 Oct;56(10):1535-43. doi: 10.1373/clinchem.2010.151043. Epub 2010 Aug 6.
Serum bilirubin has been consistently shown to be inversely related to cardiovascular disease (CVD). Recent studies showed serum bilirubin to be associated with CVD-related factors such as diabetes, metabolic syndrome, and body mass index. Although the association of serum bilirubin with CVD has been found in both retrospective and prospective studies, less information is available on the role of genes that control bilirubin concentrations and their association with CVD.
In this review, we provide detailed information on the identity of the major genes that control bilirubin concentrations and their association with serum bilirubin concentrations and CVD risk. We also update the results of the major studies that have been performed on the association between serum bilirubin, CVD, and CVD-related diseases such as diabetes or metabolic syndrome. Studies consistently indicate that bilirubin concentrations are inversely associated with different types of CVD and CVD-related diseases. A conditional linkage study indicates that UGT1A1 is the major gene controlling serum bilirubin concentrations, and this finding has been confirmed in recent genomewide association studies. Studies also indicate that individuals homozygous for UGT1A1*28 have a significantly lower risk of developing CVD than carriers of the wild-type alleles.
Serum bilirubin has a protective effect on CVD and CVD-related diseases, and UGT1A1 is the major gene controlling serum bilirubin concentrations. Pharmacologic, nonpharmacologic, or genetic interventions that increase serum bilirubin concentrations could provide more direct evidence on the role of bilirubin in CVD prevention.
血清胆红素与心血管疾病（CVD）呈负相关。最近的研究表明，血清胆红素与糖尿病、代谢综合征和体重指数等 CVD 相关因素有关。虽然在回顾性和前瞻性研究中都发现了血清胆红素与 CVD 的相关性，但关于控制胆红素浓度的基因及其与 CVD 相关性的信息较少。
在这篇综述中，我们提供了有关控制胆红素浓度的主要基因的详细信息，以及它们与血清胆红素浓度和 CVD 风险的关系。我们还更新了关于血清胆红素、CVD 和 CVD 相关疾病（如糖尿病或代谢综合征）之间关联的主要研究结果。研究一致表明，胆红素浓度与不同类型的 CVD 和 CVD 相关疾病呈负相关。条件连锁研究表明，UGT1A1 是控制血清胆红素浓度的主要基因，这一发现已在最近的全基因组关联研究中得到证实。研究还表明，UGT1A1*28 纯合子个体发生 CVD 的风险明显低于野生型等位基因携带者。
血清胆红素对 CVD 和 CVD 相关疾病具有保护作用，UGT1A1 是控制血清胆红素浓度的主要基因。增加血清胆红素浓度的药物、非药物或遗传干预措施可能为胆红素在 CVD 预防中的作用提供更直接的证据。
