Toniutto Pierluigi, Fabris Carlo, Minisini Rosalba, Apollonio Luca, Fumo Elisabetta, Caldato Maya, Smirne Carlo, Pirisi Mario
Liver Transplantation Unit, DPMSC, University of Udine, Udine, Italy.
Transplantation. 2005 May 27;79(10):1338-43. doi: 10.1097/01.tp.0000158712.42875.51.
Subjects who carry the D allele of the angiotensin-converting enzyme (ACE) gene have higher plasma and tissue angiotensin II levels, possibly concurrent with the development of obesity. In transplant recipients, treatment with calcineurin antagonists would magnify these effects. The present study verifies whether the allelic variants of ACE are a factor involved in excess weight gain after liver transplantation.
A consecutive series of 108 liver transplant recipients (73 males) were studied. Recipient ACE genotypes, determined by a polymerase chain reaction-based method, were related to body mass changes 1 year after transplant.
Body mass index (BMI) increased from the pretransplant value of 25.1+/-3.3 kg/m2 to 25.9+/-3.5 kg/m2 (P<0.005). The difference was mainly attributable to recipients carrying 1 D allele or more (N=88) in whom the BMI increased from 25.3+/-3.1 kg/m2 to 26.3+/-3.3 kg/m2 (P<0.005). A BMI of 25 kg/m or greater was measured in 30 of 45 deletion/deletion homozygotes and 25 of 43 insertion/deletion heterozygotes; in contrast, 14 of 20 insertion/insertion homozygotes had a normal body mass (P<0.01). Among patients with normal body mass pretransplant (N=56), none of 13 insertion/insertion homozygotes reached a BMI value 25 kg/m or greater posttransplant (P<0.005). At multivariate analysis, pretransplant body mass and carriage of 1 D allele or more were independent predictors of body mass gain greater than 2 kg/m.
Carriage of the D allele of the ACE gene is a strong, independent risk factor for excess weight gain after liver transplantation.
携带血管紧张素转换酶(ACE)基因D等位基因的受试者血浆和组织中的血管紧张素II水平较高,这可能与肥胖的发生有关。在移植受者中,使用钙调神经磷酸酶拮抗剂进行治疗会放大这些影响。本研究旨在验证ACE基因的等位基因变异是否是肝移植后体重过度增加的一个相关因素。
对连续的108例肝移植受者(73例男性)进行了研究。采用基于聚合酶链反应的方法确定受者的ACE基因型,并将其与移植后1年的体重变化相关联。
体重指数(BMI)从移植前的25.1±3.3kg/m²增加到25.9±3.5kg/m²(P<0.005)。这种差异主要归因于携带1个或更多D等位基因的受者(N = 88),他们的BMI从25.3±3.1kg/m²增加到26.3±3.3kg/m²(P<0.005)。45例缺失/缺失纯合子中有30例、43例插入/缺失杂合子中有25例的BMI测量值为25kg/m²或更高;相比之下,20例插入/插入纯合子中有14例体重正常(P<0.01)。在移植前体重正常的患者(N = 56)中,13例插入/插入纯合子中没有一例在移植后BMI值达到25kg/m²或更高(P<0.005)。在多变量分析中,移植前体重以及携带1个或更多D等位基因是体重增加超过2kg/m²的独立预测因素。
ACE基因D等位基因的携带是肝移植后体重过度增加的一个强烈、独立的危险因素。