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The chemokine receptor 5 Delta32 mutation is associated with increased renal survival in patients with IgA nephropathy.

Abstract：

BACKGROUND:Chemokine receptor 5 (CCR5) plays an important role in the recruitment of monocytes and T cells in inflammation and experimental studies suggest that CCR5 might be involved in the pathogenesis of IgA nephropathy. A mutation in the CCR5 gene (CCR5 Delta32), leading to a nonfunctional receptor, was recently described. We therefore evaluated the potential role of this mutation on renal survival in patients with IgA nephropathy. METHODS:The distribution of the CCR5 Delta32 genotype was determined by polymerase chain reaction (PCR) analysis in 228 patients with biopsy-proven IgA nephropathy. In 190 patients with available demographic and clinical follow-up data, the effect of the mutation on the clinical outcome was analyzed using the Log-rank test and the Cox proportional hazard model. In vitro, the influence of the CCR5 Delta32 genotype on the chemotactic response of monocytes was assessed. RESULTS:Of the 190 patients, 158 (83.2%) had a CCR5 wild-type genotype, 29 (15.3%) were heterozygous, and three patients had a homozygous CCR5 Delta32 genotype (1.6%). Renal survival was significantly longer in patients with the CCR5 Delta32 genotype than in the wild-type group (Log-rank P < 0.001). Using the multivariate Cox proportional hazard model, the CCR5 Delta32 genotype was identified as an independent factor associated with a lower risk to develop end-stage renal disease (ESRD) [hazard ratio (HR) 0.23, 95% CI 0.09 to 0.57, P= 0.002]. In vitro analysis of monocytes from CCR5 Delta32 carriers showed a reduced chemotactic response to CCR5 ligands in vitro. CONCLUSION:Our study demonstrates an independent role of the CCR5 Delta32 genotype for the clinical outcome in IgA nephropathy. In vitro experiments revealed a reduced chemotactic response of monocytes from CCR5 Delta32 carriers, thus pointing out a possible pathophysiologic explanation for the beneficial effect of the CCR5 Delta32 genotype.

journal_name

Kidney Int

journal_title

Kidney international

authors

Panzer U,Schneider A,Steinmetz OM,Wenzel U,Barth P,Reinking R,Becker JU,Harendza S,Zahner G,Fischereder M,Krämer BK,Schlöndorff D,Ostendorf T,Floege J,Helmchen U,Stahl RA

doi

10.1111/j.1523-1755.2005.00057.x

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

75-81

issue

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)50429-8

journal_volume

pub_type

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The chemokine receptor 5 Delta32 mutation is associated with increased renal survival in patients with IgA nephropathy.