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.
Dr Priya Duggal and colleagues evaluated the host genetic basis for spontaneous resolution of HCV infection.
The team performed a 2-stage, genome-wide association study in 13 international multicenter study sites.
|HLA class II is independently associated with spontaneous resolution of HCV infection|
|Annals of Internal Medicine|
The researchers evaluated 919 persons with serum HCV antibodies but no HCV RNA, and 1482 persons with serum HCV antibodies and HCV RNA.
The team evluated frequencies of 792,721 single nucleotide polymorphisms.
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, 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 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 15%, and 16% 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.
Dr Duggal's team concludes, "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."