Fat tissue accumulation during peritoneal dialysis is associated with a polymorphism in uncoupling protein 2

Background. Chronic treatment with peritoneal dialysis (PD) is a unique lon g-term metabolic procedure entailing a continuous 24-hour supply of glucose absorbed from the dialysis fluid. One common and important side effect of this treatment is weight gain and accumulation of body fat stores. However, not all patients accumulate body fat mass during PD, and the reason for th is is not clear. Recently, two new mitochondrial uncoupling proteins (UCP2 and UCP3) have been found to have thermogenic properties that suggest invol vement in the control of metabolic efficiency in humans. Moreover, recent r esults suggest that a polymorphism in the UCP2 gene may contribute to adipo se tissue accumulation through its effects on energy metabolism. It could t herefore be speculated that genetic differences in the metabolic rate might contribute to the differences in the accumulation of fat tissue during PD. Methods. Genotyping of a polymorphism in the 3' untranslated region of exon 8 of UCP2 was performed in 41 patients (53 +/- 2 years) with chronic renal failure for whom we had prospective data on body composition (as estimated by dual-energy x-ray absorptiometry) following PD. In addition, indices of dialysis adequacy, peritoneal glucose absorption, and urea kinetics were f ollowed (3 to 6 times per year in each patient) during treatment with PD. T he degree of physical activity was assessed before the start of PD. Results. Twenty patients with the deletion/deletion UCP2 genotype had a sig nificant increase in body weight (3.0 +/- 0.8 vs. -1.0 +/- 1.1 kg, P < 0.01 ) and body fat mass (3.8 +/- 0.9 vs. 0.8 +/- 1.0 kg, P < 0.05) during PD, c ompared with 19 patients with an insertion/deletion UCP2 genotype. On the o ther hand, no significant differences in indices of dialysis adequacy, peri toneal glucose absorption, urea kinetic parameters, or degree of physical a ctivity were observed when comparing patients who accumulated or lost fat t issue during PD. Conclusions. As most patients with the deletion/deletion UCP2 genotype acqu ired fat tissue during PD, the present results suggest that the UCP2 polymo rphism contributes to variations in body composition. Thus, variations in U CP2 production or activity may be factors contributing to adipose tissue ac cumulation in a subgroup of patients treated with PD. It is possible that t he polymorphism has a similar effect in the general population.