CD14-159 and -260 Gene Polymorphisms Are Associated with HBV-Related Cirrhotic Injury in Chinese Han Patients

Chun-Gen Yan；Guang-Yuan Ren；Feng Wang；Dong-Fang Zhu；Yan Zhuang

CD14 ； toll-like receptor 4 ； liver cirrhosis ； polymorphism

The Chinese Journal of Physiology

51卷2期（2008 / 04 / 01）

94 - 99

英文

The present study was to investigate the association between TLR4 mutations (Asp299Gly and Thr399Ile) and CD14 polymorphisms (base pair -159 and -260) with HBV-related cirrhosis in Chinese Han patients. By use of a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis technique, we genotyped Toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile and CD14-159 and -260 polymorphisms in 110 HBV-related cirrhotic patients and 110 healthy controls from the Chinese Han population. We found significant differences in the genotypes and allele frequencies of CD14-159 (but not -260) between healthy controls and liver cirrhotic patients, and both the CD14-159 and -260 genotypes were significantly different among Child-Pugh grades in cirrhotic patients. No TLR4 Asp299Gly and Thr399Ile mutations were detected in any cirrhotic patients or healthy controls in the Chinese Han population. These findings indicated that the polymorphisms of CD14 but not TLR4 Asp299Gly and Thr399Ile mutations may be an important genetic factor for HBV-related cirrhotic injury in the Chinese Han population.

1. Arbour, N.C.,Lorenz, E.,Schutte, B.C.,Zabner, J.,Kline, J.N.,Jones, M.,Frees, K.,Watt, J.L.,Schwartz, D.A.(2000).TLR4 mutationss are associated with endotoxin hyporesponsiveness in humans.Nat. Genet.,25,187-191.
2. Che, F.,Seokjoo, Y.,Niclas, T.,Harri, A.,Jarvela, I.,Kai, O.L.,Magnus, I.S.(2004).Hepatic expression of multiple acute phase proteins and down-regulation of nuclear receptors after acute endotoxin exposure.Biochem. Pharmacol.,67,1389-1397.
3. Clett, E.,John, S.,Ian, R.P.(2003).Monocytes heterozygous for the Asp299Gly and Thr399Ile mutations in the Toll-like receptor 4 gene show no deficit in lipopolysaccharide signalling.J. Exp. Med.,197,1787-1791.
4. Doreen, M.A.,Jacqueline, E.,Calvano, S.J.,Hahm, S.M.,Coyle, S.A.,Corbett, S.E.,Stephen, F.L.(2007).Human Toll-Like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections.J. Infect. Dis.,34,295-298.
5. Gao, H.K.,Zhou, Z.G.,Li, Y.,Chen, Y.Q.(2007).Toll-like receptor 4 Asp299Gly polymorphism is associated with an increased risk of pancreatic necrotic infection in acute pancreatitis: a study in the Chinese population.Pancreas,34,295-298.
6. Garza Gonzalez, E.,Bosques-Padilla, F.J.,Mendoza-Ibarra, S.I.,Flores-Gutierrez, J.P.,Maldonado-Garza, H.J.,Perez-Perez, G.I.(2007).Assessment of the toll-like receptor 4 Asp299gly, thr399Ile and interleukin-8-251 polymorphisms in the risk for the development of distal gastric cancer.BMC. Cancer,7,70.
7. Gonzalez-Quintela, A.,Campos, J.,Quinteiro, C.,Gude, F.(2007).Liver enzyme levels in relation to a common polymorphism in the CD14 promoter gene.Eur. J. Gastroenterol. Hepatol.,19,182-183.
8. Guo, Q.S.,Zhu, J.B.,Xia, B.(2006).Polymorphism of CD14 gene but not the mutation of TLR4 gene is associated with colorectal cancer in Chinese patients.J. Gastroenterol. Hepatol.,21,92-97.
9. Holla, L.I.,Buckova, D.,Fassmann, A.,Halabala, T.,Vasku, A.,Vacha, J.(2002).Promoter polymorphisms in the CD14 receptor gene and their potential association with the severity of chronic periodontitis.J. Med. Genet.,39,844-848.
10. Hubacek, J.A.,Rothe, G.,Pit`ha, J. C(1999).T polymorphism in the promoter of the CD14 monocyte receptor gene as a risk factor for myocardial infarction.Circulation,99,3218-3220.
11. Keskin, O.,Birben, E.,Sackesen, C.,Soyer, O.U.,Alyamac, E.,Karaaslan, C.,Tokol, N.,Ercan, H.,Kalayci, O.(2006).The effect of CD14-c159T genotypes on the cytokine response to endotoxin by peripheral blood mononuclear cells from asthmatic children.Ann. Allergy. Asthma. Immunol.,97,321-328.
12. Klein, W.,Tromm, A.,Griga, T.,Fricke, H.,Folwaczny, C.,Hocke, M.,Eitner, K.,Marx, M.,Duerig, N.,Epplen, J.T.(2002).A polymor phism in the CD14 gene is associated with Crohn disease.Scand. J. Gastroenterol.,2,189-191.
13. Laine, M, L.,Morre, S.A.,Murillo, L.S.,van Winkelhoff, A.J.,Pena, A.S.(2005).CD14 and TLR4 gene polymorphisms in adult periodontitis.J. Dent. Res.,84,1042-1046.
14. LeVan, T.D.,Bloom, J.W.,Bailey, T.J.(2001).A common single nucleotide polymorphism in the CD14 promoter decreases the affinity of Sp protein binding and enhances transcriptional activity.J. Immunol.,167,5838-5844.
15. Li,Y.,Xiong, X.Q.,Zhang, P.A.(2005).Association of C-159-T polymorphism in promoter region of CD14 and coronary heart disease.Chinese J. Med. Genetics,22,687-690.
16. Lichy, C.,Meiser, H.,Grond-Ginsbach, C.(2002).Lipopolysaccharide receptor CD14 polymorphism and risk of stroke in a South-German population.J. Neurol.,249,821-823.
17. Lorenz, E.,Hallman, M.,Marttila, R.,Ataja, R.,Schwartz, D.A.(2002).Association between the Asp299Gly polymorphisms in the Tolllike receptor 4 and premature births in the Finish population.Pediatric Res.,52,373-376.
18. Manigold, T.,Bocker, U.,Hanck, C.,Gundt, J.,Traber, P.,Antoni, C.,Rossol, S.(2003).Differential expression of toll-like receptors 2 and 4 in patients with liver cirrhosis.Eur. J. Gastroenterol. Hepatol.,159,275-282.
19. Matsumura, T.,Ito, A.,Takii, T.,Hayashi, H.,Onozaki, K.(2000).Endotoxin and cytokine regulation of toll-like receptor (TLR) 2 and TLR4 gene expression in murine liver and hepatocytes.J. Interferon Cytokine Res.,20,915-921.
20. Morre, S.A.,Murillo, L.S.,Bruggeman, C.A.,Pena, A.S.(2003).The role that the functional Asp299Gly polymorphism in the toll-like receptor-4 gene plays in susceptibility to Chlamydia trachomatis-associated tubal infertility.J. Infect. Dis.,187,341-342.
21. O`Neill, L.A.(2006).How Toll-like receptors signal: what we know and what we don`t know..Curr. Opin. Immunol.,22,303-308.
22. Obana, N.,Takahashi, S.,Kinouchi, Y.,Negoro, K.,Takagi, S.,Hiwatashi, N.,Shimosegawa, T.(2002).Ulcerative colitis is associated with a promoter polymorphism of lipopolysaccharide receptor gene, CD14.Scand. J. Gastroenterol.,6,699-704.
23. Okayama, N.,Fujimura, K.,Suehiro, Y.,Hamanaka, Y.,Fujiwara, M.,Matsubara, T.,Maekawa, T.,Hazama, S.,Oka, M.,Nohara, H.,Kayano, K.,Okita, K.,Hinoda, Y.(2002).Simple genotype analysis of the Asp299Gly polymorphism of the Toll-like receptor-4 gene that is associated with lipopolysaccharide hyporesponsiveness.J. Clin. Lab. Anal.,16,56-58.
24. Puthothu, B.,Forster, J.,Heinzmann, A.,Krueger, M.(2006).TLR-4 and CD14 polymorphisms in respiratory syncytial virus associated disease.Dis. Markers.,22,303-308.
25. Rechcinski, T.,Grebowska, A.,Kurpesa, M.,Peruga, Z.,Dziuba, M.,Krzeminska-Pakula, M.,Rudnicka, W.,Chmiela, M.(2007).CD14 gene polymorphism 159C/T in a group of patients with coronary artery disease from a population with high morbidity of cardiovascular diseases.Kardiol. Pol.,65,237-244.
26. Riordan, S.M.,Skinner, N.,Nagree, A.,McCallum, H.,McIver, C.J.,Kurtovic, J.,Hamilton, J.A.,Bengmark, S.,Williams, R.K.(2003).Peripheral blood mononuclear cell expression of toll-like receptors and relation to cytokine levels in cirrhosis.Hepatology,37,1154-1164.
27. Schwabe, R, F.,SEKI, E.,Brenner, D.A.(2006).Toll-Like Receptor Signaling in the Liver.Gastroenterology,130,1886-1900.
28. Tomasz, R.,Aneta, G.,Magorzata, K.,Zbigniew, P.,Micha, D.,Maria, K.P.,Wiesawa, R.,Magdalena, Chmiela.(2007).CD14 gene polymorphism 159C/T in a group of patients with coronary artery disease from a population with high morbidity of cardiovascular diseases.Kardiol. Pol.,65,237-244.
29. Wu, M.S.,Cheng, T.Y.,Shun, C.T.,Lin, M.T.,Chen, L.C.,Lin, J.T.(2006).Functional polymorphisms of CD14 and toll-like receptor 4 in Taiwanese Chinese with Helicobacter pylori-related gastric malignancies.Hepatogastroenterology,53,807-810.
30. Yamazaki, K.,Ueki-Maruyama, K.,Oda, T.,Tabeta, K.,Shimada, Y.,Tai, H.(2003).Single-nucleotide polymorphism in the CD14 promoter and periodontal disease expression in a Japanese population.J. Dent. Res.,82,612-616.
31. Zarember, K.A.,Godowski, P.J.(2002).Tissue expression of human Toll like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines.J. Immunol.,168,554-561.