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sTRAIL levels and TRAIL gene polymorphisms in Chinese patients with fatty liver disease

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Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily, and has been identified as a novel mediator of fatty liver disease (FLD). The aim of our study was to further investigate the relationship between TRAIL and FLD. We found that soluble TRAIL (sTRAIL) concentrations in non-alcoholic FLD (NAFLD) patients were significantly higher than those of controls, and that sTRAIL levels positively correlated with triglyceride concentrations in NAFLD patients. Our results also indicated that the AA/TT genotypes of TRAIL at 1525/1595 engendered a lower risk of FLD attack and a less severe form of steatosis for NAFLD patients in Chinese population. This study provides a means to test for susceptibility to FLD and may assist in the diagnosis of FLD. In addition, we found that 1525G/A and 1595C/T sites were in complete linkage disequilibrium in Chinese population. This might indicate a haplotype with high genetic frequency of TRAIL.

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References

  • Adams LA, Lindor KD, Angulo P (2004) The prevalence of autoantibodies and autoimmune hepatitis in patients with nonalcoholic Fatty liver disease. Am J Gastroenterol 99:1316–1320. doi:10.1111/j.1572-0241.2004.30444.x

    Article  PubMed  CAS  Google Scholar 

  • Afford SC, Adams DH (2005) Following the TRAIL from hepatitis C virus and alcohol to fatty liver. Gut 54:1518–1520. doi:10.1136/gut.2005.067801

    Article  PubMed  CAS  Google Scholar 

  • Alwayn IP, Andersson C, Lee S, Arsenault DA, Bistrian BR, Gura KM, Nose V, Zauscher B, Moses M, Puder M (2006) Inhibition of matrix metalloproteinases increases PPAR-alpha and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model. Am J Physiol Gastrointest Liver Physiol 291:G1011–G1019. doi:10.1152/ajpgi.00047.2006.0193-1857/06

    Article  PubMed  CAS  Google Scholar 

  • Anel A, Bosque A, Naval J, Pineiro A, Larrad L, Alava MA, Martinez-Lorenzo MJ (2007) Apo2L/TRAIL and immune regulation. Front Biosci 12:2074–2084

    Article  PubMed  CAS  Google Scholar 

  • Bahcecioglu IH, Yalniz M, Ataseven H, Ilhan N, Ozercan IH, Seckin D, Sahin K (2005) Levels of serum hyaluronic acid, TNF-alpha and IL-8 in patients with nonalcoholic steatohepatitis. Hepatogastroenterology 52:1549–1553

    PubMed  CAS  Google Scholar 

  • Brouwers MC, Cantor RM, Kono N, Yoon JL, van der Kallen CJ, Bilderbeek-Beckers MA, van Greevenbroek MM, Lusis AJ, de Bruin TW (2006) Heritability and genetic loci of fatty liver in familial combined hyperlipidemia. J Lipid Res 47:2799–2807. doi:10.1194/jlr.M600312-JLR200

    Article  PubMed  CAS  Google Scholar 

  • Chavin KD, Yang S, Lin HZ, Chatham J, Chacko VP, Hoek JB, Walajtys-Rode E, Rashid A, Chen CH, Huang CC, Wu TC, Lane MD, Diehl AM (1999) Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion. J Biol Chem 274:5692–5700

    Article  PubMed  CAS  Google Scholar 

  • Choi JW, Song JS, Pai SH (2004) Associations of serum TRAIL concentrations, anthropometric variables, and serum lipid parameters in healthy adults. Ann Clin Lab Sci 34:400–404

    PubMed  CAS  Google Scholar 

  • Gray HL, Sorensen EL, Hunt JS, Ober C (2001) Three polymorphisms in the 3' UTR of the TRAIL (TNF-related apoptosis-inducing ligand) gene. Genes Immun 2:469–470

    Article  PubMed  CAS  Google Scholar 

  • Han LH, Sun WS, Ma CH, Zhang LN, Liu SX, Zhang Q, Gao LF, Chen YH (2002) Detection of soluble TRAIL in HBV infected patients and its clinical implications. World J Gastroenterol 8:1077–1080

    PubMed  CAS  Google Scholar 

  • Hsiao P, Kuo K, Shin S, Yang Y, Lin W, Yang J, Chiu C, Chuang W, Tsai T, Yu M (2007) Significant correlations between severe fatty liver and risk factors for metabolic syndrome. J Gastroenterol Hepatol 22:2118–2123. doi:10.1111/j.1440-1746.2006.04698.x

    Article  PubMed  CAS  Google Scholar 

  • Kikuchi S, Miyagishi R, Fukazawa T, Yabe I, Miyazaki Y, Sasaki H (2005) TNF-related apoptosis inducing ligand (TRAIL) gene polymorphism in Japanese patients with multiple sclerosis. J Neuroimmunology 167:170–174. doi:10.1016/j.jneuroim.2005.06.021

    Article  CAS  Google Scholar 

  • Liang X, Liu Y, Zhang Q, Gao L, Han L, Ma C, Zhang L, Chen YH, Sun W (2007a) Hepatitis B virus sensitizes hepatocytes to TRAIL-induced apoptosis through Bax. J Immunol 178:503–510

    PubMed  CAS  Google Scholar 

  • Liang X, Du J, Liu Y, Cui M, Ma C, Han L, Qu Z, Zhang Z, Sun Z, Zhang L, Chen YH, Sun W (2007b) The hepatitis B virus protein MHBs(t) sensitizes hepatoma cells to TRAIL-induced apoptosis through ERK2. Apoptosis 12:1827–1836. doi:10.1007/s10495-007-0114-4

    Article  PubMed  CAS  Google Scholar 

  • Liang X, Qu Z, Zhang Z, Du J, Liu Y, Cui M, Liu H, Gao L, Han L, Liu S, Cao L, Zhao P, Sun W (2008) Blockade of preS2 down-regulates the apoptosis of HepG2.2.15 cells induced by TRAIL. Biochem Biophys Res Commun 369:456–463. doi:10.1016/j.bbrc.2008.02.035

    Article  PubMed  CAS  Google Scholar 

  • Lub-de Hooge MN, de Vries EGE, de Jong S, Bijl M (2005) Soluble TRAIL concentrations are raised in patients with systemic lupus erythematosus. Ann Rheum Dis 64:854–858. doi:10.1136/ard.2004.029058

    Article  PubMed  CAS  Google Scholar 

  • Malhi H, Barreyro FJ, Isomoto H, Bronk SF, Gores GJ (2007) Free fatty acids sensitise hepatocytes to TRAIL mediated cytotoxicity. Gut 56:1124–1131. doi:10.1136/gut.2006.118059

    Article  PubMed  CAS  Google Scholar 

  • Merriman RB, Aouizerat BE, Bass NM (2006) Genetic influences in nonalcoholic fatty liver disease. J Clin Gastroenterol 40:S30–S33

    PubMed  CAS  Google Scholar 

  • Mundt B, Wirth T, Zender L, Waltemathe M, Trautwein C, Manns MP, Kühnel F, Kubicka S (2005) Tumour necrosis factor related apoptosis inducing ligand (TRAIL) induces hepatic steatosis in viral hepatitis and after alcohol intake. Gut 54:1590–1596. doi:10.1136/gut.2004.056929

    Article  PubMed  CAS  Google Scholar 

  • Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540–543. doi:10.1126/science.7624776

    Article  PubMed  CAS  Google Scholar 

  • Poniachik J, Csendes A, Diaz JC, Rojas J, Burdiles P, Maluenda F, Smok G, Rodrigo R, Videla LA (2006) Increased production of IL-1alpha and TNF-alpha in lipopolysaccharide-stimulated blood from obese patients with non-alcoholic fatty liver disease. Cytokine 33:252–257. doi:10.1016/j.cyto.2006.02.006

    Article  PubMed  CAS  Google Scholar 

  • Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, Luketic VA, Shiffman ML, Clore JN (2001) Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 120:1183–1192

    Article  PubMed  CAS  Google Scholar 

  • Stewart SF, Vidali M, Day CP, Albano E, Jones DE (2004) Oxidative stress as a trigger for cellular immune responses in patients with alcoholic liver disease. Hepatology 39:197–203. doi:10.1002/hep.20021

    Article  PubMed  Google Scholar 

  • Tiegs G (2007) Cellular and cytokine-mediated mechanisms of inflammation and its modulation in immune-mediated liver injury. Z Gastroenterol 45:63–70. doi:10.1055/s-2006-927397

    Article  PubMed  CAS  Google Scholar 

  • Unoki M, Furuta S, Onouchi Y, Watanabe O, Doi S, Fujiwara H, Miyatake A, Fujita K, Tamari M, Nakamura Y (2000) Association studies of 33 single nucleotide polymorphisms (SNPs) in 29 candidate genes for bronchial asthma: positive association a T924C polymorphism in the thromboxane A2 receptor gene. Hum Genet 106:440–446. doi:10.1007/s004390000267

    Article  PubMed  CAS  Google Scholar 

  • Wang Q, Ji Y, Wang X, Evers BM (2000) Isolation and molecular characterization of the 5'-upstream region of the human TRAIL gene. Biochem Biophys Res Commun 276:466–471. doi:10.1006/bbrc.2000.3512

    Article  PubMed  CAS  Google Scholar 

  • Wang SH, Cao Z, Wolf JM, Van Antwerp M, Baker JR Jr (2005) Death ligand tumor necrosis factor-related apoptosis-inducing ligand inhibits experimental autoimmune thyroiditis. Endocrinology 146:4721–4726. doi:10.1210/en.2005-0627

    Article  PubMed  CAS  Google Scholar 

  • Watanabe S, Takeshige K, Muta T (2007) A cis-element in the 3'-untranslated region of IkappaB-zeta mRNA governs its stimulus-specific expression. Biochem Biophys Res Commun 356:785–791. doi:10.1016/j.bbrc.2007.03.044

    Article  PubMed  CAS  Google Scholar 

  • Weber A, Wandinger KP, Mueller W, Aktas O, Wengert O, Grundstrom E, Ehrlicha S, Windemuthc C, Kuhlmannd T, Wienker T, Bruckb W, Zipp F (2004) Identification and functional characterization of a highly polymorphic region in the human TRAIL promoter in multiple sclerosis. J Neuroimmunology 149:195–201. doi:10.1016/j.jneuroim.2003.12.014

    Article  CAS  Google Scholar 

  • Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3:673–682

    Article  PubMed  CAS  Google Scholar 

  • Willner IR, Waters B, Patil SR, Reuben A, Morelli J, Reily CA (2001) Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol 96:2957–2961. doi:10.1111/j.1572-0241.2001.04667.x

    Article  PubMed  CAS  Google Scholar 

  • Zhang XY, Zhang XD, Borrow JM, Nguyen T, Hersey P (2004) Translational control of tumor necrosis factor-related apoptosis-inducing ligand death receptor expression in melanoma cells. J Biol Chem 279:10606–10614. doi:10.1074/jbc.M308211200

    Article  PubMed  CAS  Google Scholar 

  • Zhou YJ, Li YY, Nie YQ, Ma JX, Lu LG, Shi SL, Chen MH, Hu PJ (2007) Prevalence of fatty liver disease and its risk factors in the population of South China. World J Gastroenterol 13:6419–6424. doi:10.3748/wjg.13.6156

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grant No. 30872298 for L. Gao).

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Authors and Affiliations

  1. Department of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, 250012, People’s Republic of China

    Xiaohua Yan, Liyun Xu, Jianni Qi, Xiaohong Liang, Chunhong Ma, Chun Guo, Lining Zhang, Wensheng Sun & Lifen Gao

  2. Shandong Medical College, Linyi, 276002, People’s Republic of China

    Xiaohua Yan, Jiyun Zhang & Xiaoyi Wei

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  1. Xiaohua Yan
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  2. Liyun Xu
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  3. Jianni Qi
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  4. Xiaohong Liang
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  5. Chunhong Ma
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  11. Lifen Gao
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Correspondence to Lifen Gao.

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Yan, X., Xu, L., Qi, J. et al. sTRAIL levels and TRAIL gene polymorphisms in Chinese patients with fatty liver disease. Immunogenetics 61, 551–556 (2009). https://doi.org/10.1007/s00251-009-0389-4

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  • DOI: https://doi.org/10.1007/s00251-009-0389-4

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