期刊论文详细信息
BMC Gastroenterology
Association of genetic variations in GNB1 with response to peginterferon plus ribavirin therapy for chronic hepatitis C in a Chinese population in Taiwan
Lei Wan4  Cheng-Yuan Peng3  Dong-Zong Hung6  Ni Tien2  Wen-Ling Liao1  Fuu-Jen Tsai5  Yun-Ping Lim6 
[1] Center for Personalized Medicine, China Medical University Hospital, Taichung, 40447, Taiwan;Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, 40402, Taiwan;Department of Internal Medicine, Division of Digestive System and Gastroenterology, China Medical University Hospital, Taichung, 40447, Taiwan;Genetic Center, China Medical University Hospital, Taichung, 40447, Taiwan;Department of Pediatrics, China Medical University Hospital, Taichung, 40447, Taiwan;Department of Emergency, Toxicology Center, China Medical University Hospital, Taichung, 40447, Taiwan
关键词: G protein;    Rapid virological response;    Standard of care treatment;    Hepatitis C virus;   
Others  :  858289
DOI  :  10.1186/1471-230X-12-167
 received in 2012-07-30, accepted in 2012-11-19,  发布年份 2012
PDF
【 摘 要 】

Background

The aim of this study was to evaluate whether polymorphisms in the guanine nucleotide binding (G protein), beta polypeptide 1 (GNB1) gene are associated with a rapid virological response (RVR) among HCV genotype 1 (HCV-1) and 2 (HCV-2) infected patients receiving peginterferon plus ribavirin treatment (PEG-IFNα-RBV).

Methods

We analyzed the association between RVR to PEG-IFNα-RBV therapy and 4 tagging single nucleotide polymorphisms (SNPs) of the GNB1 gene. This study included 265 HCV-1 and 195 HCV-2 infected patients in a Chinese population in Taiwan.

Results

Among the GNB1 SNPs examined, the combination of genotypes G/G and G/T populations of rs12126768 was significant inversely correlated with RVR in HCV-1 infected patients (P = 0.0330), whereas HCV-2 infected patients, combination of A/A and A/C genotypes populations at rs4648727 responded better to the PEG-IFNα-RBV treatment (P = 0.0089). However, there were no significant differences in the allele frequencies of those SNPs between RVR responders and non-responders. Several RVR susceptibility GNB1 haplotypes were identified, and the ACAT haplotype of the 4 SNPs may increase the successful outcomes of HCV-1 and HCV-2 infected patients (P = 0.0261 and P = 0.0253, respectively).

Conclusion

The data for GNB1 SNPs and the association of RVR showed that GNB1 polymorphisms might be associated with the therapeutic outcomes of HCV-1 and HCV-2 infected patients under standard of care (SOC) treatment.

【 授权许可】

   
2012 Lim et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140723100510724.pdf 883KB PDF download
77KB Image download
【 图 表 】

【 参考文献 】
  • [1]Afdhal NH, McHutchison JG, Zeuzem S, Mangia A, Pawlotsky JM, Murray JS, Shianna KV, Tanaka Y, Thomas DL, Booth DR, Goldstein DB: Pharmacogenetics and hepatitis C meeting participants. Hepatitis C pharmacogenetics: state of the art in 2010. Hepatology 2011, 53:336-345.
  • [2]Hoofnagle JH: Course and outcome of hepatitis C. Hepatology 2002, 36:S21-S29.
  • [3]Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002, 347:975-982.
  • [4]Martinot-Peignoux M, Maylin S, Moucari R, Ripault MP, Boyer N, Cardoso AC, Giuily N, Castelnau C, Pouteau M, Stern C, Aupérin A, Bedossa P, Asselah T, Marcellin P: Virological response at 4 weeks to predict outcome of hepatitis C treatment with pegylated interferon and ribavirin. Antivir Ther 2009, 14:501-511.
  • [5]Conjeevaram HS, Fried MW, Jeffers LJ, Terrault NA, Wiley-Lucas TE, Afdhal N, Brown RS, Belle SH, Hoofnagle JH, Kleiner DE, Howell CD, Virahep-C Study Group: Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1. Gastroenterology 2006, 131:470-477.
  • [6]Shiffman ML, Mihas AA, Millwala F, Sterling RK, Luketic VA, Stravitz RT, Sanyal AJ: Treatment of chronic hepatitis C virus in African Americans with genotypes 2 and 3. Am J Gastroenterol 2007, 102:761-766.
  • [7]Matsushita M, Hijikata M, Matsushita M, Ohta Y, Mishiro S: Association of mannose-binding lectin gene haplotype LXPA and LYPB with interferon-resistant hepatitis C virus infection in Japanese patients. J Hepatol 1998, 29:695-700.
  • [8]Hijikata M, Ohta Y, Mishiro S: Identification of a single nucleotide polymorphism in the MxA gene promoter (G/T at nt −88) correlated with the response of hepatitis C patients to interferon. Intervirology 2000, 43:124-127.
  • [9]Sugimoto Y, Kuzushita N, Takehara T, Kanto T, Tatsumi T, Miyagi T, Jinushi M, Ohkawa K, Horimoto M, Kasahara A, Hori M, Sasaki Y, Hayashi N: A single nucleotide polymorphism of the low molecular mass polypeptide 7 gene influences the interferon response in patients with chronic hepatitis C. J Viral Hepat 2002, 9:377-384.
  • [10]Mueller T, Gessner R, Sarrazin C, Graf C, Halangk J, Witt H, Köttgen E, Wiedenmann B, Berg T: Apolipoprotein E4 allele is associated with poor treatment response in hepatitis C virus (HCV) genotype 1. Hepatology 2003, 38:1592-1593.
  • [11]Knapp S, Hennig BJ, Frodsham AJ, Zhang L, Hellier S, Wright M, Goldin R, Hill AV, Thomas HC, Thursz MR: Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection. Immunogenetics 2003, 55:362-369.
  • [12]Matsuyama N, Mishiro S, Sugimoto M, Furuichi Y, Hashimoto M, Hijikata M, Ohta Y: The dinucleotide microsatellite polymorphism of the IFNAR1 gene promoter correlates with responsiveness of hepatitis C patients to interferon. Hepatol Res 2003, 25:221-225.
  • [13]Yee LJ, Perez KA, Tang J, van Leeuwen DJ, Kaslow RA: Association of CTLA4 polymorphisms with sustained response to interferon and ribavirin therapy for chronic hepatitis C virus infection. J Infect Dis 2003, 187:1264-1271.
  • [14]Wasmuth HE, Werth A, Mueller T, Berg T, Dietrich CG, Geier A, Gartung C, Lorenzen J, Matern S, Lammert F: Haplotype-tagging RANTES gene variants influence response to antiviral therapy in chronic hepatitis C. Hepatology 2004, 40:327-334.
  • [15]Mueller T, Mas-Marques A, Sarrazin C, Wiese M, Halangk J, Witt H, Ahlenstiel G, Spengler U, Goebel U, Wiedenmann B, Schreier E, Berg T: Influence of interleukin 12B (IL12B) polymorphisms on spontaneous and treatment-induced recovery from hepatitis C virus infection. J Hepatol 2004, 41:652-658.
  • [16]Naito M, Matsui A, Inao M, Nagoshi S, Nagano M, Ito N, Egashira T, Hashimoto M, Mishiro S, Mochida S, Fujiwara K: SNPs in the promoter region of the osteopontin gene as a marker predicting the efficacy of interferon-based therapies in patients with chronic hepatitis C. J Gastroenterol 2005, 40:381-388.
  • [17]Sarrazin C, Berg T, Weich V, Mueller T, Frey UH, Zeuzem S, Gerken G, Roggendorf M, Siffert W: GNB3 C825T polymorphism and response to interferon-alfa/ribavirin treatment in patients with hepatitis C virus genotype 1 (HCV-1) infection. J Hepatol 2005, 43:388-393.
  • [18]Tsukada H, Ochi H, Maekawa T, Abe H, Fujimoto Y, Tsuge M, Takahashi H, Kumada H, Kamatani N, Nakamura Y, Chayama K: A polymorphism in MAPKAPK3 affects response to interferon therapy for chronic hepatitis C. Gastroenterology 2009, 136:1796-1805.
  • [19]Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB: Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009, 461:399-401.
  • [20]Neves SR, Ram PT, Iyengar R: G protein pathways. Science 2002, 296:1636-1639.
  • [21]de Wilde A, Heberden C, Chaumaz G, Bordat C, Lieberherr M: Signaling networks from G beta1 subunit to transcription factors and actin remodeling via a membrane-located ER beta-related protein in the rapid action of daidzein in osteoblasts. J Cell Physiol 2006, 209:786-801.
  • [22]Hellier S, Frodsham AJ, Hennig BJ, Klenerman P, Knapp S, Ramaley P, Satsangi J, Wright M, Zhang L, Thomas HC, Thursz M, Hill AV: Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection. Hepatology 2003, 38:1468-1476.
  • [23]Simmonds P, Holmes EC, Cha TA, Chan SW, McOmish F, Irvine B, Beall E, Yap PL, Kolberg J, Urdea MS: Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 1993, 74:2391-2399.
  • [24]Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007, 81:559-575.
  • [25]Gao B, Hong F, Radaeva S: Host factors and failure of interferon-alpha treatment in hepatitis C virus. Hepatology 2004, 39:880-890.
  • [26]Ahlenstiel G, Nischalke HD, Bueren K, Berg T, Vogel M, Biermer M, Grünhage F, Sauerbruch T, Rockstroh J, Spengler U, Nattermann J: The GNB3 C825T polymorphism affects response to HCV therapy with pegylated interferon in HCV/HIV co-infected but not in HCV mono-infected patients. J Hepatol 2007, 47:348-355.
  • [27]Yu JW, Wang GQ, Sun LJ, Li XG, Li SC: Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha-2a and ribavirin. J Gastroenterol Hepatol 2007, 22:832-836.
  • [28]Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, Spengler U, Dore GJ, Powell E, Riordan S, Sheridan D, Smedile A, Fragomeli V, Müller T, Bahlo M, Stewart GJ, Booth DR, George J: IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 2009, 41:1100-1104.
  • [29]Rauch A, Kutalik Z, Descombes P, Cai T, Di Iulio J, Mueller T, Bochud M, Battegay M, Bernasconi E, Borovicka J, Colombo S, Cerny A, Dufour JF, Furrer H, Günthard HF, Heim M, Hirschel B, Malinverni R, Moradpour D, Müllhaupt B, Witteck A, Beckmann JS, Berg T, Bergmann S, Negro F, Telenti A, Bochud PY, Swiss Hepatitis C Cohort Study Swiss HIV Cohort Study: Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 2010, 138:1338-1345.
  • [30]Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M: Genome-wide association of IL28B with response to pegylatedinterferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 2009, 41:1105-1109.
  文献评价指标  
  下载次数:6次 浏览次数:24次