title: Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts.
abstract: Chinese translation
  
  
  BACKGROUND
  Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person's lifetime risk for cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and persons with genetic variants near interleukin-28B (IL-28B), the genetic basis is not well-understood.
  
  
  OBJECTIVE
  To evaluate the host genetic basis for spontaneous resolution of HCV infection.
  
  
  METHODS
  2-stage, genome-wide association study.
  
  
  METHODS
  13 international multicenter study sites.
  
  
  METHODS
  919 persons with serum HCV antibodies but no HCV RNA (spontaneous resolution) and 1482 persons with serum HCV antibodies and HCV RNA (persistence).
  
  
  METHODS
  Frequencies of 792 721 single nucleotide polymorphisms (SNPs).
  
  
  RESULTS
  Differences in allele frequencies between persons with spontaneous resolution and persistence were identified on chromosomes 19q13.13 and 6p21.32. On chromosome 19, allele frequency differences localized near IL-28B and included rs12979860 (overall per-allele OR, 0.45; P = 2.17 × 10-30) and 10 additional SNPs spanning 55 000 base pairs. On chromosome 6, allele frequency differences localized near genes for HLA class II and included rs4273729 (overall per-allele OR, 0.59; P = 1.71 × 10-16) near DQB1*03:01 and an additional 116 SNPs spanning 1 090 000 base pairs. The associations in chromosomes 19 and 6 were independent and additive and explain an estimated 14.9% (95% CI, 8.5% to 22.6%) and 15.8% (CI, 4.4% to 31.0%) of the variation in HCV resolution in persons of European and African ancestry, respectively. Replication of the chromosome 6 SNP, rs4272729, in an additional 745 persons confirmed the findings (P = 0.015).
  
  
  CONCLUSIONS
  Epigenetic effects were not studied.
  
  
  CONCLUSIONS
  IL-28B and HLA class II are independently associated with spontaneous resolution of HCV infection, and SNPs marking IL-28B and DQB1*03:01 may explain approximately 15% of spontaneous resolution of HCV infection.
authors: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Priya
authors: P
authors: Duggal
authors: Chloe L
authors: CL
authors: Thio
authors: Genevieve L
authors: GL
authors: Wojcik
authors: James J
authors: JJ
authors: Goedert
authors: Alessandra
authors: A
authors: Mangia
authors: Rachel
authors: R
authors: Latanich
authors: Arthur Y
authors: AY
authors: Kim
authors: Georg M
authors: GM
authors: Lauer
authors: Raymond T
authors: RT
authors: Chung
authors: Marion G
authors: MG
authors: Peters
authors: Gregory D
authors: GD
authors: Kirk
authors: Shruti H
authors: SH
authors: Mehta
authors: Andrea L
authors: AL
authors: Cox
authors: Salim I
authors: SI
authors: Khakoo
authors: Laurent
authors: L
authors: Alric
authors: Matthew E
authors: ME
authors: Cramp
authors: Sharyne M
authors: SM
authors: Donfield
authors: Brian R
authors: BR
authors: Edlin
authors: Leslie H
authors: LH
authors: Tobler
authors: Michael P
authors: MP
authors: Busch
authors: Graeme
authors: G
authors: Alexander
authors: Hugo R
authors: HR
authors: Rosen
authors: Xiaojiang
authors: X
authors: Gao
authors: Mohamed
authors: M
authors: Abdel-Hamid
authors: Richard
authors: R
authors: Apps
authors: Mary
authors: M
authors: Carrington
authors: David L
authors: DL
authors: Thomas
mesh_terms: D001741:Black or African American / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics* / Q000821:virology; D018937:Hepatitis C Antibodies; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood; D012075:Remission, Spontaneous; D000095022:Interferon Lambda
chemical_list: D059866:HLA-DQ beta-Chains; D018937:Hepatitis C Antibodies; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C069051:HLA-DQB1 antigen; C000624353:interferon-lambda, human; D000095022:Interferon Lambda