title: The impact of polymorphisms in STAT6 on treatment outcome in HCV infected Taiwanese Chinese.
abstract: Genetic polymorphisms observed in various disease states associated with sensitivity or resistance to specific treatments have been a robust area of investigation for decades, with the potential to allow clinicians to make evidence-based decisions on the appropriate course of treatment. This study aimed to evaluate whether genetic polymorphisms of the signal transducer and activator of transcription 6 gene (STAT6) could be associated with a sustained virological response (SVR) among patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2) who were treated with peginterferon plus ribavirin (PEG-IFNα-RBV). We analyzed the associations between SVR to PEG-IFNα-RBV therapy and 4 single nucleotide polymorphisms (SNPs) in STAT6. This study included Taiwanese Chinese patients infected with either HCV-1 (n = 265) or HCV-2 (n = 195) in the presence or absence of an SVR. Among the STAT6 SNPs examined, the dosage effect of the A allele and allele frequency in rs1059513 were inversely correlated with SVR in patients infected with HCV-1 (P = 0.0179 and P = 0.0235, respectively). This effect was not observed in patients infected with HCV-2. The GG, GGG, and GGGC STAT6 haplotypes comprising 2, 3, and 4 SNPs (rs1059513, rs703817, rs324015, and rs3024974) were found to be associated with SVR, and their presence may increase the probability of a successful treatment outcome in patients infected with HCV-1 (P = 0.0273, 0.0352, and 0.0368, respectively). Moreover, a multivariate logistic regression model for predicting an SVR revealed that the presence of the GGGC haplotype carriers mutually affected the outcome of PEG-IFNα-RBV treatment. The presence of STAT6 SNPs and the association with SVR demonstrated that STAT6 polymorphisms might influence the therapeutic outcomes of patients infected with HCV-1 under standard-of-care (SOC) treatment.
authors: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
authors: Yun-Ping
authors: YP
authors: Lim
authors: Yu-An
authors: YA
authors: Hsu
authors: Kun-Hsi
authors: KH
authors: Tsai
authors: Fuu-Jen
authors: FJ
authors: Tsai
authors: Cheng-Yuan
authors: CY
authors: Peng
authors: Wen-Ling
authors: WL
authors: Liao
authors: Dong-Zong
authors: DZ
authors: Hung
authors: Ni
authors: N
authors: Tien
authors: Chien-Yih
authors: CY
authors: Lin
authors: Lei
authors: L
authors: Wan
mesh_terms: D044466:Asian People / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D050800:STAT6 Transcription Factor / Q000235:genetics*; D013624:Taiwan; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D011994:Recombinant Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
references: J Immunol. 2002 Feb 1;168(3):996-1000
references: 11801631
references: Immunity. 1996 Mar;4(3):313-9
references: 8624821
references: Immunity. 2005 Jul;23(1):19-28
references: 16039576
references: J Gen Virol. 1993 Nov;74 ( Pt 11):2391-9
references: 8245854
references: J Cell Mol Med. 2008 Jun;12(3):876-88
references: 18494930
references: Cancer Immunol Immunother. 2004 Feb;53(2):86-91
references: 14593499
references: J Exp Med. 2005 Jun 20;201(12):1899-903
references: 15967820
references: Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10800-5
references: 10485906
references: Gastroenterology. 2010 Jan;138(1):116-22
references: 19852964
references: Hepatology. 1994 Jul;20(1 Pt 1):15-20
references: 8020885
references: Oncogene. 2000 May 15;19(21):2577-84
references: 10851056
references: Hepatology. 2004 Apr;39(4):880-90
references: 15057887
references: World J Gastroenterol. 2007 May 7;13(17):2436-41
references: 17552026
references: Minerva Gastroenterol Dietol. 2004 Mar;50(1):1-7
references: 15719001
references: Hepatology. 2009 Mar;49(3):763-74
references: 19140155
references: Cell. 2011 Oct 14;147(2):436-46
references: 22000020
references: Immunity. 1995 Jun;2(6):689-97
references: 7796300
references: J Hepatol. 2011 Apr;54(4):629-39
references: 21129804
references: J Surg Res. 2004 Nov;122(1):14-20
references: 15522309
references: Lancet. 2001 Sep 22;358(9286):958-65
references: 11583749
references: Ann Hepatol. 2003 Jul-Sep;2(3):135-9
references: 15115965
references: Minerva Gastroenterol Dietol. 2005 Mar;51(1):15-29
references: 15756151
references: Bioinformatics. 2005 Jan 15;21(2):263-5
references: 15297300
references: J Hepatol. 2010 Jun;52(6):827-31
references: 20400194
references: Eur J Immunol. 2009 May;39(5):1252-9
references: 19338001
references: Nature. 2005 Aug 18;436(7053):939-45
references: 16107833
references: Am J Hum Genet. 2007 Sep;81(3):559-75
references: 17701901
references: Lancet Infect Dis. 2005 Sep;5(9):558-67
references: 16122679
references: Future Microbiol. 2006 Jun;1(1):103-12
references: 17661689
references: N Engl J Med. 2002 Sep 26;347(13):975-82
references: 12324553