Association between CXCL10 and DPP4 Gene Polymorphisms and a Complementary Role for Unfavorable IL28B Genotype in Prediction of Treatment Response in Thai Patients with Chronic Hepatitis C Virus Infection.
Pretreatment serum levels of interferon-γ-inducible protein-10 (IP-10, CXCL10) and dipeptidyl peptidase-4 (DPP IV) predict treatment response in chronic hepatitis C (CHC). The association between functional genetic polymorphisms of CXCL10 and DPP4 and treatment outcome has not previously been studied. This study aimed to determine the association between genetic variations of CXCL10 and DPP4 and the outcome of treatment with pegylated interferon-α (PEG-IFN-α) based therapy in Thai patients with CHC. 602 Thai patients with CHC treated using a PEG-IFN-α based regimen were genotyped for CXCL10 rs56061981 G>A and IL28B rs12979860 C>T. In addition, in patients infected with CHC genotype 1, DPP4 (rs13015258 A>C, rs17848916 T>C, rs41268649 G>A, and rs 17574 T>C) were genotyped. Correlations between single nucleotide polymorphisms, genotype, and treatment response were analyzed. The rate of sustained virologic response (SVR) was higher for the CC genotype of IL28B rs12979860 polymorphisms than for non-CC in both genotype 1 (60.6% vs. 29.4%, P < 0.001) and non-genotype 1 (69.4% vs. 49.1%, P < 0.05) CHC. SVR was not associated with the CXCL10 gene variant in all viral genotypes or DPP4 gene polymorphisms in viral genotype1. Multivariate analysis revealed IL28B rs12979860 CC genotype (OR = 3.12; 95% CI, 1.72-5.67; P < 0.001), hepatitis C virus RNA < 400,000 IU/ml (OR = 2.21; 95% CI, 1.22-3.99, P < 0.05), age < 45 years (OR = 2.03; 95% CI, 1.11-3.68; P < 0.05), and liver fibrosis stage 0-1 (OR = 1.64; 95% CI, 1.01-2.65, P < 0.05) were independent factors for SVR. Unfavorable IL28B rs12979860 CT or TT genotypes with the CXCL10 rs56061981 non-GG genotype were associated with a higher SVR than GG genotype (66.7% vs. 33.0%, P = 0.004) in viral genotype 1. In Thai CHC genotype 1 infected patients with an unfavorable IL28B rs12979860 CT/TT genotype, the complementary CXCL10 polymorphism strongly enhances prediction of treatment response.
Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Kessarin
K
Thanapirom
Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Sirinporn
S
Suksawatamnuay
Gastroenterology Unit, Department of Medicine, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Wattana
W
Sukeepaisarnjaroen
Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Pisit
P
Tangkijvanich
Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Sombat
S
Treeprasertsuk
Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Panarat
P
Thaimai
Center of Excellence in Clinical Virology Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Rujipat
R
Wasitthankasem
Center of Excellence in Clinical Virology Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Yong
Y
Poovorawan
Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Piyawat
P
Komolmit
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D054357:Chemokine CXCL10 / Q000235:genetics* / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics* / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D015398:Signal Transduction; D013785:Thailand; D016896:Treatment Outcome; D000095022:Interferon Lambda
D000998:Antiviral Agents; D054357:Chemokine CXCL10; D018819:Dipeptidyl Peptidase 4; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C114753:CXCL10 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C042807:DPP4 protein, human; C100416:peginterferon alfa-2a