Nordfors L, Heimbürger O, Lönnqvist F, Lindholm B, Helmrich J, Schalling M, Stenvinkel P
Department of Neurogenetics, Karolinska Hospital, Huddinge University Hospital, Huddinge, Sweden.
Kidney Int. 2000 Apr;57(4):1713-9. doi: 10.1046/j.1523-1755.2000.00016.x.
Chronic treatment with peritoneal dialysis (PD) is a unique long-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 this is not clear. Recently, two new mitochondrial uncoupling proteins (UCP2 and UCP3) have been found to have thermogenic properties that suggest involvement in the control of metabolic efficiency in humans. Moreover, recent results suggest that a polymorphism in the UCP2 gene may contribute to adipose tissue accumulation through its effects on energy metabolism. It could therefore be speculated that genetic differences in the metabolic rate might contribute to the differences in the accumulation of fat tissue during PD.
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 followed (3 to 6 times per year in each patient) during treatment with PD. The degree of physical activity was assessed before the start of PD.
Twenty patients with the deletion/deletion UCP2 genotype had a significant 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, compared with 19 patients with an insertion/deletion UCP2 genotype. On the other hand, no significant differences in indices of dialysis adequacy, peritoneal glucose absorption, urea kinetic parameters, or degree of physical activity were observed when comparing patients who accumulated or lost fat tissue during PD.
As most patients with the deletion/deletion UCP2 genotype acquired fat tissue during PD, the present results suggest that the UCP2 polymorphism contributes to variations in body composition. Thus, variations in UCP2 production or activity may be factors contributing to adipose tissue accumulation in a subgroup of patients treated with PD. It is possible that the polymorphism has a similar effect in the general population.
腹膜透析（PD）的长期治疗是一种独特的长期代谢过程，需要持续24小时从透析液中吸收葡萄糖。这种治疗常见且重要的副作用之一是体重增加和体内脂肪储存的积累。然而，并非所有接受PD治疗的患者都会积累体脂，其原因尚不清楚。最近，发现两种新的线粒体解偶联蛋白（UCP2和UCP3）具有产热特性，提示它们参与人体代谢效率的调控。此外，最近的研究结果表明，UCP2基因的多态性可能通过影响能量代谢而导致脂肪组织的积累。因此，可以推测代谢率的遗传差异可能导致PD治疗期间脂肪组织积累的差异。
对41例慢性肾衰竭患者（53±2岁）进行UCP2基因外显子8的3'非翻译区多态性基因分型，我们有这些患者PD治疗后身体成分的前瞻性数据（通过双能X线吸收法估算）。此外，在PD治疗期间，对透析充分性、腹膜葡萄糖吸收和尿素动力学指标进行随访（每位患者每年3至6次）。在PD开始前评估身体活动程度。
与19例插入/缺失UCP2基因型患者相比，20例缺失/缺失UCP2基因型患者在PD治疗期间体重（3.0±0.8 vs. -1.0±1.1 kg，P<0.01）和体脂量（3.8±0.9 vs. 0.8±1.0 kg，P<0.05）显著增加。另一方面，比较PD治疗期间积累或减少脂肪组织的患者时，在透析充分性指标、腹膜葡萄糖吸收、尿素动力学参数或身体活动程度方面未观察到显著差异。
由于大多数缺失/缺失UCP2基因型患者在PD治疗期间获得了脂肪组织，目前的结果表明UCP2多态性导致身体成分的差异。因此，UCP2产生或活性的差异可能是导致接受PD治疗的亚组患者脂肪组织积累的因素。这种多态性在普通人群中可能有类似的作用。
