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Relationship of elevated bilirubin level with subclinical atherosclerosis and oxidative stress in Gilbert syndrome

Busra Copur, Nisbet Yilmaz, Canan Topcuoglu, Emrullah Kiziltunc, Mustafa Cetin, Turan Turhan, Burak Furkan Demir, Emin Altiparmak, Ihsan Ates




            Aim: This study aims to determine oxidant status and left ventricular mass index (LVMI) and their relationship with mild hyperbilirubinemia in patients with Gilbert syndrome (GS).

Materials and Methods: A total of 84 patients, including 41 (48.8%) patients with GS and 43 (51.2%) patients without GS, were included in the study. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were studied for oxidant status.

Results: TAS was found to be higher in the GS patients compared to the non-GS patients (1.7±0.1 vs. 1.5±0.2; p=0.002); there was no significant difference between the groups in terms of mean TOS and mean OSI (p>0.05). No significant difference was observed between the GS and non-GS patients in terms of mean left ventricular volume and mean LVMI (p>0.05). However, subgroup analysis based on sex showed that GS patients had lower LVMI for both sexes. In GS patients, TAS level had a positive correlation with albumin (r=0.319; p=0.042), triglyceride (r=0.392; p=0.011), total bilirubin (r=0.420; p=0.006), direct bilirubin (r=0.361; p=0.020), and indirect bilirubin (r=0.338; p=0.0311) levels; no correlation was revealed between TAS level and other laboratory findings (p>0.05). The regression model showed that risk factors of direct bilirubin (?±SE=0.13±0.03; p<0.001), uric acid (?±SE=0.04±0.01; p=0.001), and albumin (?±SE=0.17±0.04; p<0.001) were independent predictors of TAS level.

Conclusion: This study revealed a relationship between mild hyperbilirubinemia and antioxidant balance in GS. Although statistical significance was not reached, LVMI was found to be lower in the GS group compared to the non-GS group for both sexes.


Gilbert syndrome; hyperbilirubinemia; oxidative stress; subclinical atherosclerosis


Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med. 1995;333(18):1171-5.

Akboga MK, Canpolat U, Sahinarslan A, Alsancak Y, Nurkoc S, Aras D, et al. Association of serum total bilirubin level with severity of coronary atherosclerosis is linked to systemic inflammation. Atherosclerosis. 2015;240(1):110-4.

Vitek L. Bilirubin and atherosclerotic diseases. Physiol Res. 2017;66(Supplementum 1):S11-S20.

Baranano DE, Rao M, Ferris CD, Snyder SH. Biliverdin reductase: a major physiologic cytoprotectant. Proc Natl Acad Sci U S A. 2002;99(25):16093-8.

Sedlak TW, Snyder SH. Bilirubin benefits: cellular protection by a biliverdin reductase antioxidant cycle. Pediatrics. 2004;113(6):1776-82.

Sedlak TW, Snyder SH. Cycling the wagons for biliverdin reductase. J Biol Chem. 2009;284(46):le11; author reply le2.

Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. 2005;38(12):1103-11.

Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57(6):450-8.

Ulas T, Buyukhatipoglu H, Kirhan I, Dal MS, Ulas S, Demir ME, et al. Evaluation of oxidative stress parameters and metabolic activities of nurses working day and night shifts. Revista da Escola de Enfermagem da U S P. 2013;47(2):471-6.

Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. N Engl J Med. 2001;344(8):581-90.

Benaron DA, Bowen FW. Variation of initial serum bilirubin rise in newborn infants with type of illness. Lancet. 1991;338(8759):78-81.

Aycicek A, Erel O, Kocyigit A. Decreased total antioxidant capacity and increased oxidative stress in passive smoker infants and their mothers. Pediatr Int. 2005;47(6):635-9.

Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, et al. Hyperbilirubinemia, augmentation of endothelial function, and decrease in oxidative stress in Gilbert syndrome. Circulation. 2012;126(5):598-603.

Vitek L, Jirsa M, Brodanova M, Kalab M, Marecek Z, Danzig V, et al. Gilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels. Atherosclerosis. 2002;160(2):449-56.

Stocker R, Keaney JF, Jr. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004;84(4):1381-478.

Meisinger C, Baumert J, Khuseyinova N, Loewel H, Koenig W. Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population. Circulation. 2005;112(5):651-7.

Bowry VW, Stanley KK, Stocker R. High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma from fasting donors. Proc Natl Acad Sci U S A. 1992;89(21):10316-20.

Wang H, Wu L, Reinhard BM. Scavenger receptor mediated endocytosis of silver nanoparticles into J774A.1 macrophages is heterogeneous. ACS Nano. 2012;6(8):7122-32.

Ates I, Ozkayar N, Altay M, Yilmaz F, Topcuoglu C, Al???k M, et al. Is disulphide/thiol ratio related to blood pressure ?n masked hypertension? Clinical and experimental hypertension.

Ates I, Ozkayar N, Inan B, Yilmaz FM, Topcuoglu C, Neselioglu S, et al. Dynamic thiol/disulphide homeostasis in patients with newly diagnosed primary hypertension. Journal of the American Society of Hypertension : JASH. 2016;10(2):159-66.

Ates I, Ozkayar N, Topcuoglu C, Dede F. Relationship between oxidative stress parameters and asymptomatic organ damage in hypertensive patients without diabetes mellitus. Scandinavian Cardiovascular Journal. 2015(0):1-23.

Balamir I, Ates I, Topcuoglu C, Turhan T. Association of Endocan, Ischemia-Modified Albumin, and hsCRP Levels With Endothelial Dysfunction in Type 2 Diabetes Mellitus. Angiology. 2017:3319717740781.

Kundi H, Ates I, Kiziltunc E, Cetin M, Cicekcioglu H, Neselioglu S, et al. A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. The American journal of emergency medicine. 2015.

Li WC, Mo LJ, Shi X, Lin ZY, Li YY, Yang Z, et al. Antioxidant status of serum bilirubin, uric acid and albumin in pemphigus vulgaris. Clin Exp Dermatol. 2018;43(2):158-63.

MC C. Lipid Profili, Serum Ürik Asit, Glukoz ve ?nsulin Direnci Üzerine Gilbert's Sendromunun Etkileri. Cukurova Medical Journal. 2014;39(3):443-50.

Yesilova Z, Serdar M, Ercin CN, Gunay A, Kilciler G, Hasimi A, et al. Decreased oxidation susceptibility of plasma low density lipoproteins in patients with Gilbert's syndrome. J Gastroenterol Hepatol. 2008;23(10):1556-60.

DOI: https://doi.org/10.22037/ghfbb.v13i2.1684