Analysis of <em>IL28B</em> Variants in an Egyptian Population Defines the 20 Kilobases Minimal Region Involved in Spontaneous Clearance of Hepatitis C Virus

<div><p>Spontaneous clearance of hepatitis C virus (HCV) occurs in ∼30% of acute infections. Host genetics play a major role in HCV clearance, with a strong effect of single nucleotide polymorphisms (SNPs) of the <em>IL28B</em> gene already found in different populations, mostly infected with viral genotypes 1 and 3. Egypt has the highest prevalence of HCV infection in the world, which is mostly due to viral genotype 4. We investigated the role of several <em>IL28B</em> SNPs in HCV spontaneous clearance in an Egyptian population. We selected nine SNPs within the <em>IL28B</em> genomic region covering the linkage disequilibrium (LD) block known to be associated with HCV clearance in European populations. These SNPs were genotyped in 261 HCV-infected Egyptian subjects (130 with spontaneous clearance and 131 with chronic infection). The most associated SNPs were rs12979860 (P = 1.6×10⁻⁷) and the non-synonymous <em>IL28B</em> SNP, rs8103142 (P = 1.6×10⁻⁷). Interestingly, three SNPs at the two bounds of the region were monomorphic, reducing the size of the LD block in which the causal variants are potentially located to ∼20 kilobases. HCV clearance in Egypt was associated with a region of <em>IL28B</em> smaller than that identified in European populations, and involved the non-synonymous <em>IL28B</em> SNP, rs8103142.</p>