Chudek Jerzy, Szotowska Magdalena, Karkoszka Henryk, Verbeke Francis, Trautsolt Wanda, Gumprecht Janusz, Vanholder Raymond, Wiecek Andrzej
Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia in Katowice, Katowice, Poland and Department of Pathophysiology, Medical University of Silesia in Katowice, Katowice, Poland.
Ann Transplant. 2013 Nov 4;18:593-603. doi: 10.12659/AOT.884022.
Low plasma adiponectin concentration was recently recognized as a novel risk factor for new-onset diabetes after transplantation. Pharmacological modulation of the renin-angiotensin system activity and genetic predisposition were shown to have an influence on plasma adiponectin level. Therefore the aim of this study is to analyze the association between angiotensin-converting enzyme (ACE) I/D, angiotensin II type 1 receptor (AT1R) A1166C and angiotensinogen (AGT) M235T genotypes and plasma adiponectin concentration as well as insulin resistance in a cohort of kidney transplant patients.
MATERIAL/METHODS: AGT M235T, ACE I/D and AT1R A1166C genotyping and plasma adiponectin and insulin concentrations assessment were performed in 372 patients with functioning kidney allograft (eGFR >20 ml/min/1.73 m2) from 2 transplant centres.
Females with II ACE I/D genotype had a significantly higher plasma adiponectin concentration than the ID+DD subgroup, which could partially be explained by a lower BMI in the II subgroup. Males with TT genotype of the AGT M235T gene polymorphism (and higher BMI) had higher plasma concentration of insulin and HOMAIR values than those in the MT+MM subgroup. A multiple regression analysis revealed that only female sex (b=0.239), BMI (b=–0.208) and ACE II genotype (b=0.129) were significantly associated with plasma adiponectin concentration variability. A similar analysis for HOMA-IR showed that its variability was associated with BMI (b=0.333), eGFR (b=–0.115) and plasma adiponectin concentration (b=–0.064) irrespective of any of the analyzed genotypes.
Plasma adiponectin concentration, but not insulin resistance, seems to be modulated only by ACE I/D polymorphism in kidney transplant patients. Polymorphisms of the other renin-angiotensin system components do not influence plasma adiponectin concentration or insulin resistance in these patients.
血浆脂联素浓度降低最近被认为是移植后新发糖尿病的一个新的危险因素。肾素-血管紧张素系统活性的药物调节和遗传易感性已被证明对血浆脂联素水平有影响。因此,本研究的目的是分析血管紧张素转换酶(ACE)I/D、血管紧张素II 1型受体(AT1R)A1166C和血管紧张素原(AGT)M235T基因多态性与一组肾移植患者血浆脂联素浓度以及胰岛素抵抗之间的关联。
材料/方法:对来自2个移植中心的372例具有功能的肾移植受者(估算肾小球滤过率>20 ml/min/1.73 m2)进行AGT M235T、ACE I/D和AT1R A1166C基因分型以及血浆脂联素和胰岛素浓度评估。
具有II型ACE I/D基因型的女性血浆脂联素浓度显著高于ID+DD亚组,这部分可以用II亚组较低的体重指数来解释。具有AGT M235T基因多态性TT基因型(且体重指数较高)的男性血浆胰岛素浓度和稳态模型评估胰岛素抵抗(HOMAIR)值高于MT+MM亚组。多元回归分析显示,只有女性性别(b=0.239)、体重指数(b=-0.208)和ACE II基因型(b=0.129)与血浆脂联素浓度变异性显著相关。对HOMA-IR进行的类似分析表明,其变异性与体重指数(b=0.333)、估算肾小球滤过率(b=-0.115)和血浆脂联素浓度(b=-0.064)相关,而与任何分析的基因型无关。
在肾移植患者中,血浆脂联素浓度似乎仅受ACE I/D多态性调节,而胰岛素抵抗不受其调节。肾素-血管紧张素系统其他成分的多态性不会影响这些患者的血浆脂联素浓度或胰岛素抵抗。