Two novel SNPs associated with HCV-induced fibrosis progression

Only a fraction of patients with chronic HCV infection develop liver fibrosis, a process that might also be affected by genetic factors. We studied well-characterized HCV-infected patients of European descent who underwent liver biopsies before treatment.

We defined various liver fibrosis phenotypes on the basis of METAVIR scores, with and without taking the duration of HCV infection into account. Our GWA analyses were conducted on a primary cohort of ~1200 patients using 780K single nucleotide polymorphisms (SNPs). We genotyped 96 SNPs with P values <5 × 10?5 from an independent replication cohort of ~1200 patients. In the combined cohort of ~2400 HCV-infected patients, the SNPs rs16851720 (in the total sample) and rs4374383 (in patients who received blood transfusions) were associated with fibrosis progression (Pcombined = 8.9 × 10?9 and 1.1 × 10?9, respectively). The SNP rs16851720 is located within RNF7, which encodes an antioxidant that protects against apoptosis. SNP rs4374383 is linked to the functionally related gene MERTK, which encode factors involved in phagocytosis of apoptotic cells by macrophages. Our GWA study identified several susceptibility loci for HCV-induced liver fibrosis; these were linked to genes that regulate apoptosis. Apoptotic control might therefore be involved in liver fibrosis.