Clinical Advances in Liver, Pancreas, and Biliary TractGenetic Variation in IL28B Is Associated With Chronic Hepatitis C and Treatment Failure: A Genome-Wide Association Study
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Patients and Methods
Patients were included from the Swiss Hepatitis C Cohort Study and the Swiss HIV Cohort Study, 2 multicenter studies performed at 8 major Swiss hospitals and their local affiliated centers,30, 31 and from the Medical Clinic for Hepatology and Gastroenterology, Medical University Charité Campus, Virchow–Klinikum Berlin, in Berlin, Germany. Written informed consent, including genetic testing, was mandatory for inclusion, and the study was approved by all local ethical committees. Due to the
Chronic Versus Spontaneously Cleared HCV Infection
The study included 1362 patients with HCV infection, among whom 347 had spontaneously cleared HCV infection and 1015 had progressed to persistent infection; 914 were HCV mono-infected and 448 were coinfected with HIV/HCV (Supplementary Table 2). Several SNPs near the IL28 locus on chromosome 19 were associated with chronic HCV infection with genome-wide significance (Figure 1). The top hit rs8099917 (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.74–3.06; P = 6.07 × 10−9; Figure 1) is
Discussion
This is the first genome-wide association study to report the influence of human genetic variation on the natural control of HCV infection. We found a similar effect of the same genetic marker (rs8099917, located near the IL28B gene) for both natural and treatment-induced control of HCV infection. The lowest carriage frequency of the risk allele (24%) was observed among persons with spontaneous clearance and increased to 32% among chronically infected patients who responded to treatment and to
Acknowledgments
The members of the Swiss Hepatitis C and HIV Cohort Studies are listed in the supplementary material.
A.R. and Z.K. contributed equally to this study, as did S.B., F.N., A.T., and P.-Y.B.
The authors thank Martin Rickenbach; Sandrine Estoppey for data management; Isabelle Durussel for genotyping; Anne–Laure Chanson, Arnold Probst, Ivana Rubino, and Thierry Roger for logistic assistance; Millan Ortiz for haplotype analysis; Thierry Calandra for support in all steps of the study and critical review
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Conflicts of interest The authors disclose no conflicts.
Funding The Swiss Hepatitis C and HIV Cohort Studies are supported by the Swiss National Science Foundation (3347C0-108782/1, grant nos. 3347-069366, 3247-116862, and 3100AO-116323/1, and Swiss HIV Cohort Study grant 543), the Swiss Federal Office for Education and Sciences (03.0599), and the European Commission (LSHM-CT-2004-503359; VIRGIL Network of Excellence on Antiviral Drug Resistance). Genotyping in the Swiss Hepatitis C Cohort Study and statistical analyses were supported by the Leenaards Foundation and Debiopharm S.A. Genotyping in the Swiss HIV Cohort Study was supported by an unrestricted grant by Essex Chemie AG, the Novaris Research Foundation, and Infectigen, Switzerland. P.-Y.B. is supported by the Swiss National Science Foundation (32003B_127613/1), and the Leenaards Foundation.