IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study.
<h4>Background</h4>To date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIF...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2011
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/35e1fae1f2ff4e0fbdcb58e851dcbeeb |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:35e1fae1f2ff4e0fbdcb58e851dcbeeb |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:35e1fae1f2ff4e0fbdcb58e851dcbeeb2021-11-04T05:37:23ZIL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study.1549-12771549-167610.1371/journal.pmed.1001092https://doaj.org/article/35e1fae1f2ff4e0fbdcb58e851dcbeeb2011-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21931540/?tool=EBIhttps://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>To date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R). Viral clearance is achieved in 40%-50% of patients. Interleukin 28B (IL28B) genotype predicts treatment-induced and spontaneous clearance. To improve the predictive value of this genotype, we studied the combined effect of variants of IL28B with human leukocyte antigen C (HLA-C), and its ligands the killer immunoglobulin-like receptors (KIR), which have previously been implicated in HCV viral control.<h4>Methods and findings</h4>We genotyped chronic hepatitis C (CHC) genotype 1 patients with PegIFN/R treatment-induced clearance (n = 417) and treatment failure (n = 493), and 234 individuals with spontaneous clearance, for HLA-C C1 versus C2, presence of inhibitory and activating KIR genes, and two IL28B SNPs, rs8099917 and rs12979860. All individuals were Europeans or of European descent. IL28B SNP rs8099917 "G" was associated with absence of treatment-induced clearance (odds ratio [OR] 2.19, p = 1.27×10(-8), 1.67-2.88) and absence of spontaneous clearance (OR 3.83, p = 1.71×10(-14), 2.67-5.48) of HCV, as was rs12979860, with slightly lower ORs. The HLA-C C2C2 genotype was also over-represented in patients who failed treatment (OR 1.52, p = 0.024, 1.05-2.20), but was not associated with spontaneous clearance. Prediction of treatment failure improved from 66% with IL28B to 80% using both genes in this cohort (OR 3.78, p = 8.83×10(-6), 2.03-7.04). There was evidence that KIR2DL3 and KIR2DS2 carriage also altered HCV treatment response in combination with HLA-C and IL28B.<h4>Conclusions</h4>Genotyping for IL28B, HLA-C, and KIR genes improves prediction of HCV treatment response. These findings support a role for natural killer (NK) cell activation in PegIFN/R treatment-induced clearance, partially mediated by IL28B.Vijayaprakash SuppiahSilvana GaudieriNicola J ArmstrongKate S O'ConnorThomas BergMartin WeltmanMaria Lorena AbateUlrich SpenglerMargaret BassendineGregory J DoreWilliam L IrvingElizabeth PowellMargaret HellardStephen RiordanGail MatthewsDavid SheridanJacob NattermannAntonina SmedileTobias MüllerEmma HammondDavid DunnFrancesco NegroPierre-Yves BochudSimon MallalGolo AhlenstielGraeme J StewartJacob GeorgeDavid R BoothInternational Hepatitis C Genetics Consortium (IHCGC)Public Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 8, Iss 9, p e1001092 (2011) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R |
| spellingShingle |
Medicine R Vijayaprakash Suppiah Silvana Gaudieri Nicola J Armstrong Kate S O'Connor Thomas Berg Martin Weltman Maria Lorena Abate Ulrich Spengler Margaret Bassendine Gregory J Dore William L Irving Elizabeth Powell Margaret Hellard Stephen Riordan Gail Matthews David Sheridan Jacob Nattermann Antonina Smedile Tobias Müller Emma Hammond David Dunn Francesco Negro Pierre-Yves Bochud Simon Mallal Golo Ahlenstiel Graeme J Stewart Jacob George David R Booth International Hepatitis C Genetics Consortium (IHCGC) IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study. |
| description |
<h4>Background</h4>To date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R). Viral clearance is achieved in 40%-50% of patients. Interleukin 28B (IL28B) genotype predicts treatment-induced and spontaneous clearance. To improve the predictive value of this genotype, we studied the combined effect of variants of IL28B with human leukocyte antigen C (HLA-C), and its ligands the killer immunoglobulin-like receptors (KIR), which have previously been implicated in HCV viral control.<h4>Methods and findings</h4>We genotyped chronic hepatitis C (CHC) genotype 1 patients with PegIFN/R treatment-induced clearance (n = 417) and treatment failure (n = 493), and 234 individuals with spontaneous clearance, for HLA-C C1 versus C2, presence of inhibitory and activating KIR genes, and two IL28B SNPs, rs8099917 and rs12979860. All individuals were Europeans or of European descent. IL28B SNP rs8099917 "G" was associated with absence of treatment-induced clearance (odds ratio [OR] 2.19, p = 1.27×10(-8), 1.67-2.88) and absence of spontaneous clearance (OR 3.83, p = 1.71×10(-14), 2.67-5.48) of HCV, as was rs12979860, with slightly lower ORs. The HLA-C C2C2 genotype was also over-represented in patients who failed treatment (OR 1.52, p = 0.024, 1.05-2.20), but was not associated with spontaneous clearance. Prediction of treatment failure improved from 66% with IL28B to 80% using both genes in this cohort (OR 3.78, p = 8.83×10(-6), 2.03-7.04). There was evidence that KIR2DL3 and KIR2DS2 carriage also altered HCV treatment response in combination with HLA-C and IL28B.<h4>Conclusions</h4>Genotyping for IL28B, HLA-C, and KIR genes improves prediction of HCV treatment response. These findings support a role for natural killer (NK) cell activation in PegIFN/R treatment-induced clearance, partially mediated by IL28B. |
| format |
article |
| author |
Vijayaprakash Suppiah Silvana Gaudieri Nicola J Armstrong Kate S O'Connor Thomas Berg Martin Weltman Maria Lorena Abate Ulrich Spengler Margaret Bassendine Gregory J Dore William L Irving Elizabeth Powell Margaret Hellard Stephen Riordan Gail Matthews David Sheridan Jacob Nattermann Antonina Smedile Tobias Müller Emma Hammond David Dunn Francesco Negro Pierre-Yves Bochud Simon Mallal Golo Ahlenstiel Graeme J Stewart Jacob George David R Booth International Hepatitis C Genetics Consortium (IHCGC) |
| author_facet |
Vijayaprakash Suppiah Silvana Gaudieri Nicola J Armstrong Kate S O'Connor Thomas Berg Martin Weltman Maria Lorena Abate Ulrich Spengler Margaret Bassendine Gregory J Dore William L Irving Elizabeth Powell Margaret Hellard Stephen Riordan Gail Matthews David Sheridan Jacob Nattermann Antonina Smedile Tobias Müller Emma Hammond David Dunn Francesco Negro Pierre-Yves Bochud Simon Mallal Golo Ahlenstiel Graeme J Stewart Jacob George David R Booth International Hepatitis C Genetics Consortium (IHCGC) |
| author_sort |
Vijayaprakash Suppiah |
| title |
IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study. |
| title_short |
IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study. |
| title_full |
IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study. |
| title_fullStr |
IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study. |
| title_full_unstemmed |
IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study. |
| title_sort |
il28b, hla-c, and kir variants additively predict response to therapy in chronic hepatitis c virus infection in a european cohort: a cross-sectional study. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/35e1fae1f2ff4e0fbdcb58e851dcbeeb |
| work_keys_str_mv |
AT vijayaprakashsuppiah il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT silvanagaudieri il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT nicolajarmstrong il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT katesoconnor il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT thomasberg il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT martinweltman il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT marialorenaabate il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT ulrichspengler il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT margaretbassendine il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT gregoryjdore il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT williamlirving il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT elizabethpowell il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT margarethellard il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT stephenriordan il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT gailmatthews il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT davidsheridan il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT jacobnattermann il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT antoninasmedile il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT tobiasmuller il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT emmahammond il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT daviddunn il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT francesconegro il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT pierreyvesbochud il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT simonmallal il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT goloahlenstiel il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT graemejstewart il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT jacobgeorge il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT davidrbooth il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy AT internationalhepatitiscgeneticsconsortiumihcgc il28bhlacandkirvariantsadditivelypredictresponsetotherapyinchronichepatitiscvirusinfectioninaeuropeancohortacrosssectionalstudy |
| _version_ |
1718445201600544768 |