|
|
|
|
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
|
|
|
|
|
|
|
|
نویسنده
|
suppiah v. ,gaudieri s. ,armstrong n.j. ,o'connor k.s. ,berg t. ,weltman m. ,abate m.l. ,spengler u. ,bassendine m. ,dore g.j. ,irving w.l. ,powell e. ,hellard m. ,riordan s. ,matthews g. ,sheridan d. ,nattermann j. ,smedile a. ,müller t. ,hammond e. ,dunn d. ,negro f. ,bochud p.-y. ,mallal s. ,ahlenstiel g. ,stewart g.j. ,george j. ,booth d.r.
|
|
منبع
|
plos medicine - 2011 - دوره : 8 - شماره : 9
|
|
چکیده
|
Background: 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. methods and findings: 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. conclusions: 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. © 2011 suppiah et al.
|
|
|
|
|
آدرس
|
storr liver unit,westmead millennium institute,university of sydney,sydney,australia,institute for immunology and allergy research,westmead millennium institute,university of sydney,sydney, Australia, institute for infectious diseases,murdoch university,perth, Australia, cancer research program,garvan institute for medical research,university of new south wales,sydney,australia,school of mathematics and statistics,university of new south wales,sydney, Australia, institute for immunology and allergy research,westmead millennium institute,university of sydney,sydney, Australia, medizinische klinik m.s. hepatologie und gastroenterologie,universitätsmedizin berlin,campus virchow-klinikum,charité,germany,department of hepatology,clinic for gastroenterology and rheumatology,university clinic leipzig,leipzig, Germany, department of gastroenterology and hepatology,nepean hospital,sydney, Australia, liver physiopathology lab,department of internal medicine,university of turin,turin, Italy, department of internal medicine i,university of bonn,bonn, Germany, liver research group,institute of cellular medicine,medical school,newcastle university,newcastle upon tyne, United Kingdom, national centre in hiv epidemiology and clinical research,university of new south wales,sydney,australia,st vincent's hospital,sydney, Australia, nihr biomedical research unit in gastroenterology and the liver,university of nottingham,nottingham, United Kingdom, princess alexandra hospital,department of gastroenterology and hepatology,woolloongabba,australia,the university of queensland,school of medicine,princess alexandra hospital,woolloongabba,qld, United States, burnet institute,commercial road,melbourne,vic, Australia, gastrointestinal and liver unit,prince of wales hospital and university of new south wales,sydney, Australia, national centre in hiv epidemiology and clinical research,university of new south wales,sydney,australia,st vincent's hospital,sydney, Australia, liver research group,institute of cellular medicine,medical school,newcastle university,newcastle upon tyne, United Kingdom, department of internal medicine i,university of bonn,bonn, Germany, liver physiopathology lab,department of internal medicine,university of turin,turin, Italy, medizinische klinik m.s. hepatologie und gastroenterologie,universitätsmedizin berlin,campus virchow-klinikum,charité,germany,department of hepatology,clinic for gastroenterology and rheumatology,university clinic leipzig,leipzig, Germany, institute for infectious diseases,murdoch university,perth, Australia, institute for infectious diseases,murdoch university,perth, Australia, divisions of gastroenterology,hepatology,and clinical pathology,university hospitals geneva, Switzerland, divisions of gastroenterology,hepatology,and clinical pathology,university hospitals geneva, Switzerland, institute for infectious diseases,murdoch university,perth, Australia, storr liver unit,westmead millennium institute,university of sydney,sydney, Australia, institute for immunology and allergy research,westmead millennium institute,university of sydney,sydney, Australia, storr liver unit,westmead millennium institute,university of sydney,sydney, Australia, institute for immunology and allergy research,westmead millennium institute,university of sydney,sydney, Australia
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|