The chemokine receptor 5 Delta32 mutation is associated with increased renal survival in patients with IgA nephropathy.
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The chemokine receptor 5 Delta32 mutation is associated with increased renal survival in patients with IgA nephropathy. / Panzer, Ulf; Schneider, André; Steinmetz, Oliver M; Wenzel, Ulrich; Barth, Petra; Reinking, Rüdiger; Becker, Jan U; Harendza, Sigrid; Zahner, Gunther; Fischereder, Michael; Krämer, Bernhard K; Krämer, Bernhard H; Schlöndorff, Detlef; Ostendorf, Tammo; Floege, Jürgen; Helmchen, Udo; Stahl, Rolf A K.
in: KIDNEY INT, Jahrgang 67, Nr. 1, 1, 2005, S. 75-81.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - The chemokine receptor 5 Delta32 mutation is associated with increased renal survival in patients with IgA nephropathy.
AU - Panzer, Ulf
AU - Schneider, André
AU - Steinmetz, Oliver M
AU - Wenzel, Ulrich
AU - Barth, Petra
AU - Reinking, Rüdiger
AU - Becker, Jan U
AU - Harendza, Sigrid
AU - Zahner, Gunther
AU - Fischereder, Michael
AU - Krämer, Bernhard K
AU - Krämer, Bernhard H
AU - Schlöndorff, Detlef
AU - Ostendorf, Tammo
AU - Floege, Jürgen
AU - Helmchen, Udo
AU - Stahl, Rolf A K
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 67
SP - 75
EP - 81
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 1
M1 - 1
ER -
