Genetic and clinical factors influence the baseline permeability of the peritoneal membrane.
BACKGROUND
Patients starting peritoneal dialysis (PD) show a significant variability in small solute transport across the peritoneal membrane (PM). The latter parameter determines dialysis prescription and survival. Clinical factors probably influence solute transport across the PM, but the putative role of genetic variants is unknown.


METHODS
We have investigated the influence of functional polymorphisms of VEGF, ENOS, and IL-6, together with clinical and biological factors, on baseline peritoneal equilibration test (PET) parameters in a homogeneous population of 152 unrelated Caucasian PD patients from Belgium and the North of France.


RESULTS
The distribution of the 21 alleles (7 polymorphisms) and linkage disequilibrium parameters were similar in PD patients and healthy subjects. Univariate and multivariate analyses identified comorbidity, serum albumin, and the -174G/C polymorphism of IL-6 as independent predictors of small solute transport. The -174G/C polymorphism of IL-6 was associated with significantly higher IL-6 mRNA levels in the PM and higher plasma and dialysate IL-6 concentrations, suggesting a dominant effect of the C allele. Patients harboring the CC and GC genotypes (N= 92) were characterized by significantly higher permeability parameters and inflammatory markers than patients harboring the GG genotype (N= 60). In contrast with IL-6, VEGF and ENOS polymorphisms had no influence on baseline peritoneal permeability.


CONCLUSIONS
These data (1) show that, together with clinical parameters, the functionally relevant -174G/C polymorphism of IL-6 contributes to the interpatient variability in small solute transport rate at the start of PD; and (2) substantiate the critical role played by IL-6 in the PM.
Gillerot
Gaëlle
G
Division of Nephrology, and Division of Epidemiology and Statistics, Université Catholique de Louvain Medical School, Brussels, Belgium.
Goffin
Eric
E
Michel
Catherine
C
Evenepoel
Pieter
P
Biesen
Wim Van
WV
Tintillier
Michel
M
Stenvinkel
Peter
P
Heimbürger
Olof
O
Lindholm
Bengt
B
Nordfors
Louise
L
Robert
Annie
A
Devuyst
Olivier
O
D000328:Adult; D000368:Aged; D001692:Biological Transport; D005260:Female; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000378:metabolism*; D010539:Permeability; D011110:Polymorphism, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III