Clinical significance of the CCR5delta32 allele in hepatitis C.

BACKGROUND The CCR5 receptor, expressed on Th1 cells, may influence clinical outcomes of HCV infection. We explored a possible link between a CCR5 32-base deletion (CCR5delta32), resulting in the expression of a non-functioning receptor, and clinical outcomes of HCV infection. METHODS CCR5 and HCV-related phenotypes were analysed in 1,290 chronically infected patients and 160 patients with spontaneous clearance. RESULTS Carriage of the CCR5delta32 allele was observed in 11% of spontaneous clearers compared to 17% of chronically infected patients (OR = 0.59, 95% CI interval 0.35-0.99, P = 0.047). Carriage of this allele also tended to be observed more frequently among patients with liver inflammation (19%) compared to those without inflammation (15%, OR = 1.38, 95% CI interval 0.99-1.95, P = 0.06). The CCR5delta32 was not associated with sustained virological response (P = 0.6), fibrosis stage (P = 0.8), or fibrosis progression rate (P = 0.4). CONCLUSIONS The CCR5delta32 allele appears to be associated with a decreased rate of spontaneous HCV eradication, but not with hepatitis progression or response to antiviral therapy.

Allele-specific polymerase chain reaction diagnostic test for the functional MDR1 polymorphism in dogs

The major multidrug transporter P-glycoprotein (Pgp) contributes to the barrier function of several tissues and organs, including the brain. In a subpopulation of Collies and seven further dog breeds, a 4 base pair deletion has been described in the Pgp-encoding MDR1 gene. This deletion results in the absence of a functional form of Pgp and loss of its protective function. Severe intoxication with the Pgp substrate ivermectin has been attributed to the genetically determined lack of Pgp. An allele-specific polymerase chain reaction (PCR)-based screening method has been developed to detect the mutant allele and to determine if a dog is homozygous or heterozygous for the mutation. Based on this validation, the allele-specific PCR proved to be a robust, reproducible and specific tool, allowing rapid determination of the MDR1 genotype of dogs of at risk breeds using blood samples or buccal swabs.