Genotypes of the renin-angiotensin system and glucocorticoid complications
Genotypes of the renin-angiotensin system and glucocorticoid complications
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DOI：
10.1111/ped.12434
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发表时间：
2015-02-01
影响因子：
1.4
通讯作者：
Nakamura, Akio
中科院分区：
文献类型：
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作者：
Nakamura, Akio
背景血管紧张素原（AGT）和血管紧张素转换酶（ACE）被认为是体重指数（BMI）和全身血压（BP）的重要调节剂。 AGT 和 ACE 基因的这些单核苷酸多态性 (SNP) 与肥胖或高血压之间的关联已被确定。本研究检查了接受糖皮质激素治疗肾病综合征的儿童中 AGT 和 ACE 基因的分子变异与体重或血压之间的关系。 方法 对 20 名日本儿童（男性，n = 14；女性，n = 6；年龄，2-13 岁）进行 AGT 多态性（M235T 和 A-6G）和 ACE 多态性（插入/缺失：I/D 和RS4341）。所有研究的儿童均每日接受泼尼松龙 2 毫克/公斤治疗，持续 4 周，随后隔日接受泼尼松龙治疗，持续 8 周。研究期间对各组患者的BMI、BMI z评分、血脂、肾功能和血压进行评估。结果糖皮质激素治疗期间的BMI和BMI z评分在AGT M235T多态性的TT基因型和AGT A-6G多态性的AA基因型中显着高于其他基因型（P < 0.05）。相比之下，ACE I/D 和 rs4341 基因型的分子变异在糖皮质激素暴露期间没有改变体重。然而，很明显，AGT和ACE多态性对血压、血脂和肾功能没有显着影响。结论AGT M235T多态性的TT基因型和A-6G多态性的AA基因型可能使儿童在最初接受糖皮质激素治疗肾病综合征时容易出现体重增加。
BackgroundAngiotensinogen (AGT) and angiotensin-converting enzyme (ACE) are recognized as important regulators of body mass index (BMI) and systemic blood pressure (BP). An association between these single nucleotide polymorphisms (SNP) of AGT and ACE genes and obesity or hypertension has been established. This study examined relationships between the molecular variants of the AGT and ACE genes and bodyweight or BP in children treated with glucocorticoids for nephrotic syndrome.MethodsTwenty Japanese children (male, n = 14; female, n = 6; age, 2-13years) were genotyped for AGT polymorphisms (M235T and A-6G) and the ACE polymorphisms (insertion/deletion: I/D and rs4341). All of the children studied were treated with daily prednisolone 2mg/kg for 4weeks and thereafter alternate-day prednisolone for 8weeks. BMI, BMI z-scores, blood lipids, renal function and BP in each group were evaluated during the study period.ResultsBMI and BMI z-scores during the glucocorticoid therapy were significantly higher in the TT genotype of the AGT M235T polymorphisms and the AA genotype of the AGT A-6G polymorphisms compared to other genotypes (P < 0.05). In contrast, the molecular variant of ACE I/D and rs4341 genotypes did not change bodyweight during the glucocorticoid exposure. It was evident, however, that the BP and blood lipids and renal function were not significantly influenced by the AGT and ACE polymorphisms.ConclusionsThe TT genotype of the AGT M235T and the AA genotype of the A-6G polymorphisms may predispose children to bodyweight gain when initially treated with glucocorticoids for nephrotic syndrome.