Epidemiology

CCR5 polymorphism tied to hepatitis C virus clearance

Last Updated: 2005-08-01 14:40:18 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Heterozygosity of the CCR5 delta 32 genotype is significantly associated with spontaneous hepatitis C viral (HCV) clearance as well as reduced hepatic inflammation, Irish researchers report in the August issue of Gut.

Among the clinical implications of the findings "is that the anti-CCR5 directed medication may offer a potential treatment for HCV -- although more studies on this polymorphism would have to be done first, in relation to impact on other HCV genotypes," lead investigator Dr. Carol A. Goulding told Reuters Health.

Dr. Goulding of St. James' Hospital, Dublin and colleagues came to this conclusion after studying 283 women who were exposed to HCV genotype 1b from a single source via contaminated anti-D immunoglobulin in 1977.

The researchers note that chemokines have a significant role in lymphocyte recruitment and trafficking, and inherited variations in CCR2, CCR5 and the ligand RANTES might have influenced the response to this HCV exposure. To investigate, the team genotyped these subjects and another 120 unselected controls.

No relationship was found between CCR2 or RANTES and response to HCV. However, CCR5 delta 32 heterozygotes were more likely (odds ratio, 1.83) to have had spontaneous clearance of the virus than were those without the mutation.

In previous work, the researchers found that HLA DRB1*3011 positivity was associated with reduced hepatic inflammation. Nevertheless, no additive effect was seen with CCR5 delta 32, suggesting, say the investigators, a dominant role for this HLA allele.

The heterozygous genotype was found in about 18% of HCV-infected subjects and controls. There was only one homozygote found in each group.

The researchers suggest that the effect of this mutation may not only be important in those with HCV, but also "to the vast number who are coinfected with HIV," particularly in light of the anti-CCR5 agents being investigated in these patients.

Gut 2005;54:1157-1161.