Polymorphisms of the uridine-diphosphoglucuronosyltransferase 1A1 gene and coronary artery disease : Cellular and Molecular Biology Letters Jump to ContentJump to Main Navigation
Show Summary Details

Cellular and Molecular Biology Letters

Editor-in-Chief: /


IMPACT FACTOR increased in 2015: 1.753

SCImago Journal Rank (SJR) 2015: 0.788
Source Normalized Impact per Paper (SNIP) 2015: 0.645
Impact per Publication (IPP) 2015: 1.748

99,00 € / $149.00 / £75.00*

Online
ISSN
1689-1392
See all formats and pricing



Select Volume and Issue
Loading journal volume and issue information...

Polymorphisms of the uridine-diphosphoglucuronosyltransferase 1A1 gene and coronary artery disease

1Chung-Hwa University of Medical Technology, 89, Wen-Hwa 1st Street, Tainan, Taiwan

2Chi-Mei Medical Center, 901, Chung-Hwa Road, Tainan, Taiwan

3Department of Pathology, Chi-Mei Medical Center, 901, Chung-Hwa Road, Tainan, Taiwan

© 2007 University of Wrocław, Poland. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. (CC BY-NC-ND 3.0)

Citation Information: Cellular and Molecular Biology Letters. Volume 13, Issue 1, Pages 1–10, ISSN (Online) 1689-1392, DOI: 10.2478/s11658-007-0030-1, October 2007

Publication History

Published Online:
2007-10-19

Abstract

Bilirubin, an antioxidant in the blood, plays a role in protection from atherosclerosis. The level of bilirubin is highly correlated to the incidence of coronary artery disease (CAD). Unconjugated bilirubin is conjugated with glucuronic acid through the reaction of uridine 5′-diphosphate-glucuronosyl transferase 1A1 (UGT1A1). The interactions of CAD and the variations in the coding regions of the UGT1A1 gene have never been evaluated. The purpose of this study was to analyze the influence of the UGT1A1 variant on the incidence of CAD. There were 135 participants in this study: 61 in the experimental group, who had CAD, and 74 in the control group, who did not have CAD. The blood samples from all 135 participants were collected and assayed to clarify the relationship between bilirubin and CAD. The assay of the polymerase chain reaction and the sequence of the UGT1A1 gene were examined to find the gene’s polymorphisms. The bilirubin levels for the participants in the control group were significantly higher than for the patients in the CAD group. Although the concentration of bilirubin in the UGT1A1 variant was higher than the wild type for the patients in the CAD group, there was no significant difference in the polymorphism of UGT1A1 between the patients in the CAD group and the participants in the control group.

Keywords: Atherosclerosis; Coronary artery disease; UGT1A1; Bilirubin; Antioxidant

  • [1] Dudnik, L.B. and Khrapova, N.G. Characterization of bilirubin inhibitory properties in free radical oxidation reactions. Membr. Cell Biol. 12 (1998) 233–240.

  • [2] Neuzil, J. and Stocker, R. Free and albumin-bound bilirubin are efficient coantioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J. Biol. Chem. 269 (1994) 16712–16719.

  • [3] Nakagami, T., Toyomura, K., Kinoshita, T. and Morisawa, S. A beneficial role of bile pigments as an endogenous tissue protector: anti-complement effects of biliverdin and conjugated bilirubin. Biochim. Biophys. Acta 1158 (1993) 189–193.

  • [4] Mayer, M. Association of serum bilirubin concentration with risk of coronary artery disease. Clin. Chem. 4611 (2000) 1723–1727.

  • [5] Schwertner, H.A., Jackson, W.G. and Tolan, G. Association of low serum concentration of bilirubin with increased risk of coronary artery disease. Clin. Chem. 40 (1994) 18–23.

  • [6] Wu, T.W. Is serum bilirubin a risk factor for coronary artery disease? Clin. Chem. 40 (1994) 9–10.

  • [7] Schwertner, H.A and Joseph, R.F. Jr. Comparison of various lipid, lipoprotein, and bilirubin combinations as risk factors for predicting coronary artery disease. Atherosclerosis 150 (2000) 381–387. http://dx.doi.org/10.1016/S0021-9150(99)00387-1 [CrossRef]

  • [8] Hunt, S.C., Kronenberg, F., Eckfeldt, J.H., Hopkins, P.N., Myers, R.H. and Heiss G. Association of plasma bilirubin with coronary heart disease and segregation of bilirubin as a major gene trait: the NHLBI family heart study. Atherosclerosis 154 (2001) 747–754. http://dx.doi.org/10.1016/S0021-9150(00)00420-2 [CrossRef]

  • [9] Hopkins, P.N., Wu, L.L., Hunt, S.C., James, B.C., Vincent, G.M. and Williams, R.R. Higher serum bilirubin associated with decreased risk for early familial coronary artery disease. Arterioscler. Thromb. Vasc. Biol. 16 (1996) 250–255. [CrossRef]

  • [10] Breimer, L.H., Wannamethee, G., Ebrahim, S. and Shaper, A.G. Serum bilirubin and risk of ischemic heart disease in middle-aged British men. Clin. Chem. 41 (1995) 1504–1508.

  • [11] Endler, G., Hamwi, A., Sunder-Plassmann, R., Exner, M., Vukovich, T., Mannhaleter, C., Wojta, J., Huber, K. and Wagner, O. Is low serum bilirubin an independent risk factor for coronary artery disease in men but not in women? Clin. Chem. 49 (2003) 1201–1204. http://dx.doi.org/10.1373/49.7.1201 [CrossRef]

  • [12] Bosma, P.J. Inherited disorders of bilirubin metabolism. J. Hepatol. 38 (2003) 107–117. http://dx.doi.org/10.1016/S0168-8278(02)00359-8 [CrossRef]

  • [13] Ritter, J.K., Crawfoed, J.M. and Owens, I.S. Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells. J. Biol. Chem. 266 (1991) 1043–1047.

  • [14] Bosma, P.J., Seppen, J., Goldhoorn, B., Bakker, C., Oude Elferink RPJ., Chowdhury, J.R., Chowdhury, N.R. and Jansen, P.L. Bilirubin UDPglucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J. Biol. Chem. 269 (1994) 17960–17964.

  • [15] Huang, C.S., Luo, G.A., Huang, M.J, Yu, S.C. and Yang, S.S. Variations of the bilirubin uridine-diphosphoglucuronosyl transferase 1 A1 gene in healthy Taiwanese. Pharmacogenetics 10 (2000) 539–544. http://dx.doi.org/10.1097/00008571-200008000-00007 [CrossRef]

  • [16] Raijalers, M.T.M., Jamsem, P.L.M., Steegers, E.A.P. and Peters, W.H.M. Association of human liver bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter region of the UGT1A1 gene. J. Hepatol. 33 (2000) 348–351. http://dx.doi.org/10.1016/S0168-8278(00)80268-8 [CrossRef]

  • [17] Ando, Y., Chida, M., Nakayama, K., Saka, H. and Kamataki, T. The UGT1A1*28 allele is relatively rare in a Japanese population. Pharmacogenetics 8 (1998) 357–360. http://dx.doi.org/10.1097/00008571-199808000-00010 [CrossRef]

  • [18] Beutler, E., Gelbart, T. and Demina, A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: A balanced polymorphism for regulation of bilirubin metabolism? Proc. Natl. Acad. Sci. USA. 95 (1998) 8170–8174. http://dx.doi.org/10.1073/pnas.95.14.8170 [CrossRef]

  • [19] Maruo, Y., Poon, K.K.H., Oto, M., Iwai, M., Takahashi, H., Mori, A., Sato, H. and Takeuchi, Y. Co-occurrence of three different mutations in the bilirubin UDP-glucuronosyltransferase gene in a Chinese family with Crigler-Najjar syndrome type I and Gilbert’s syndrome. Clin. Genet. 64 (2003) 420–423. http://dx.doi.org/10.1034/j.1399-0004.2003.00136.x [CrossRef]

  • [20] Maruo, Y., Nishizawa, K., Sato, H., Sawa, H. and Shimada, M. Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate-glucuronosyltransferase gene. Pediatrics 106 (2000) 59–62. http://dx.doi.org/10.1542/peds.106.5.e59 [CrossRef]

  • [21] Kadakol, A., Ghosh, S.S., Sappal, B.S., Sharma, G., Chowdhury, J.R. and Chowdhury, N.R. Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype. Human Mutation 16 (2000) 297–306. http://dx.doi.org/10.1002/1098-1004(200010)16:4<297::AID-HUMU2>3.0.CO;2-Z [CrossRef]

  • [22] Miners, J.O., McKinnon, R.A. and Mackenzie, P.I. Genetic polymorphisms of UDP-glucuronosyltransferases and their functional significance. Toxicology 181–182 (2002) 453–456. http://dx.doi.org/10.1016/S0300-483X(02)00449-3 [CrossRef]

  • [23] Ciotti, M., Chen, F., Rubaltelli, F.F. and Owens, I.S. Coding defect and a TATA box mutation at the bilirubin UDP-glucuronosyltransferase gene cause Crigler-Najjar type I disease. Biochim. Biophys. Acta 1407 (1998) 40–50.

  • [24] Galbraith, R. Heme oxygenase: who needs it? Exp. Biol. Med. 222 (1999) 299–305. http://dx.doi.org/10.1046/j.1525-1373.1999.d01-147.x [CrossRef]

  • [25] Tenhunen, R., Marver, H.S. and Shcmid, R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. P.N.A.S. 61 (1968) 748–755. http://dx.doi.org/10.1073/pnas.61.2.748 [CrossRef]

  • [26] Maines, M.D. The heme osygenase system: a regulator of second messenger gases. Annu. Rev. Pharmacol. Toxicol. 37 (1997) 517–554. http://dx.doi.org/10.1146/annurev.pharmtox.37.1.517 [CrossRef]

  • [27] Watanabe, Y., Nakajima, M., Ohashi, N., Kume, T. and Yokoi, T. Glucuronidation of etoposide in human liver microsomes is specifically catalyzed by UDP-glucuronosyltransferase 1A1. Drug Metab. Dispos. 31 (2003) 589–595. http://dx.doi.org/10.1124/dmd.31.5.589 [CrossRef]

  • [28] Shimizu, M., Tsuyuki, A., Yamamoto, C., Ohta, K., Matsushita, R., Suzuki, K., Matsumoto, Y. and Masamichi, F. Effects of Aspirin and/or salicylate on hydrolysis and glucuronidation of indomethacin in rat erythrocytes and hepatocytes. Biol. Pharm. Bull. 26 (2003) 675–682. http://dx.doi.org/10.1248/bpb.26.675 [CrossRef]

  • [29] Pruesaritanont, T., Subramanian, R., Xiaojun, Fang, Ma, B., Qiu, Y., Lin, J.H., Pearson, P.G. and Baillie, T.A. Glucuronidation of statins in animals and humans: A novel mechanism of statin lactonization. Drug Metab. Dispos. 30 (2002) 505–512. http://dx.doi.org/10.1124/dmd.30.5.505 [CrossRef]

  • [30] Wierzbicki, A.S. and Crook, M.A. Cholestatic liver dysfunction. Lancet 354 (1999) 954. http://dx.doi.org/10.1016/S0140-6736(05)75706-8 [CrossRef]

  • [31] Buchwald, H., Williams, S.E., Matts, J.P. and Boen, J.R. Lipid modulation and liver function tests. A report of the Program on the surgical control of hyperlipidemia (POSCH). J. Cardiovasc. Risk. 9 (2002) 83–87. http://dx.doi.org/10.1097/00043798-200204000-00003 [CrossRef]

  • [32] Grosser, N., Abate, A., Oberle, S., Verman, H.J., Dennery, P.A., Becker, J.C., Pohle, T., Seidman, D.S. and Schroder, H. Heme oxygenase-1 induction may explain the antioxidant profile of aspirin. Biochim. Biophys. Res. Commun. 308 (2003) 956–960. http://dx.doi.org/10.1016/S0006-291X(03)01504-3 [CrossRef]

  • [33] Grosser, N., Hemmerle, A., Berndt, G., Erdamm, L., Jomlelmann, U., Schurger, S., Wijayanti, N., Immenschuh, S. and Shroder, H. The antioxidant defense protein heme oxygenase 1 is a novel target for statins in endothelial cells. Free Rad. Biol. Med. 37 (2004) 2064–2071. http://dx.doi.org/10.1016/j.freeradbiomed.2004.09.009

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Amit Goel and Rakesh Aggarwal
Journal of Gastroenterology and Hepatology, 2013, Volume 28, Number 11, Page 1687
[2]
S. Stender, R. Frikke-Schmidt, B. G. Nordestgaard, P. Grande, and A. Tybjaerg-Hansen
Journal of Internal Medicine, 2013, Volume 273, Number 1, Page 59
[3]
Keizo Ohnaka and Suminori Kono
Expert Review of Endocrinology & Metabolism, 2010, Volume 5, Number 6, Page 891
[4]
Dariusz Plewczyński and Krzysztof Ginalski
Cellular and Molecular Biology Letters, 2009, Volume 14, Number 1, Page 1

Comments (0)

Please log in or register to comment.