Frequency of the HIV-protective CC chemokine receptor 5-Δ32/Δ32 genotype is increased in hepatitis C

Background & Aims: A homozygous 32-base pair deletion in the CCR5 gene (CCR5-Δ32) protects against human immunodeficiency virus infection (HIV). However, the role of this mutation in other infections, such as hepatitis C virus (HCV) infection, has not been defined. Methods: We determined the frequency of the CCR5-Δ32 mutation by polymerase chain reaction in anti-HCV⁺ (n = 153), anti-HIV⁺ (n = 102), and anti-HCV⁺/ HIV⁺ (n = 130) white patients as well as in 102 healthy blood donors. Then, HIV and HCV loads, aminotransferases, and CD4 and CD8 cell counts were compared between the resulting subsets of CCR5-Δ32/wild-type heterozygotes, CCR5-Δ32, and wild-type homozygotes, respectively. Results: Twelve of 153 (7.8%) anti-HCV-seropositive patients and 1 of 102 (1.0%) healthy blood donors were CCR5-Δ32 homozygous, whereas CCR5-Δ32 homozygosity was absent in anti-HIV⁺ and anti-HCV⁺/HIV⁺ patients (P < 0.001). The frequency of the CCR5-Δ32 allele was higher in the anti-HCV⁺ (16.0%, P < 0.05) and anti-HCV⁺/HIV⁺ (12.7%, NS) patients than in healthy blood donors (8.3%) and anti-HIV⁺ patients (9.3%), respectively. Anti-HCV⁺ CCR5-Δ32 homozygotes occurred 3 times more frequently than expected from the Hardy-Weinberg equation (P < 0.0001) and had significantly higher HCV loads than wild-type patients (P = 0.045). Conclusions: The increased prevalence of CCR5-Δ32 homozygosity associated with increased viral loads in patients with chronic hepatitis C suggests that the CCR5-Δ32 mutation may be an adverse host factor in hepatitis C.