부산대학교 도서관

Background: Chemokines and their receptors are important mediators of leucocyte trafficking and are suggested to be critical for establishment of inflammatory autoimmune processes. CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4+ T cells. We hypothesised that the CCR5delta(Δ)32 genotype, which impairs surface expression of CCR5 in heterozygotes and is linked to a functional polymorphism of CD45RA expressed on suppressor-inducer-like `naïve' CD4+ T cells, may modulate the inflammatory process in primary biliary cirrhosis (PBC). Methods: CCR5Δ32 polymorphism was determined by PCR in 226 Caucasian PBC patients and 197 racially matched controls from two geographical areas, Newcastle, UK and Padua, Italy. (UK: 144 PBC, 105 controls, Italy: 82 PBC, 92 controls). Results: When the two series were analysed separately, there were no significant differences in the genotype distribution comparing patients and controls (UK: wt/wt 72% vs 76%; wt/Δ32 28% vs 22%; Δ32/Δ32 0% vs 2%, P = 0.24; Italy: wt/wt 72% vs 82%; wt/Δ32 27% vs 17%; Δ32/Δ32 0% vs 1%, P 0.14). However, when the data for the two series were pooled and reanalysed, we found an increase in the CCR5Δ32 mutation in PBC patients vs controls (28% vs 21%, OR 1.43, P 0.03), but there was no evidence that this Δ32 polymorphism is associated with less severe disease. Conclusions: Although this two-centre genetic association study is large compared with others performed in PBC, taken separately, each geographically based cohort of patients and controls is underpowered to detect a small effect of this functional polymorphism. This emphasises the need for far larger case-control collections to address which polymorphic markers or haplotypes might modify the pathogenesis and clinical course of PBC. We propose that multi-centre collaboration on an international scale in `orphan' complex liver diseases such as (PBC) is supported by the International Association for the Study of the Liver and promoted via their journal with development of a brief format for web-based publication of studies. [ABSTRACT FROM AUTHOR]