Genotypes of the renin–angiotensin system and glucocorticoid complications

BACKGROUND: Angiotensinogen (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. METHODS: Twenty Japanese children (male, n = 14; female, n = 6; age, 2-13 years) 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 2 mg/kg for 4 weeks and thereafter alternate-day prednisolone for 8 weeks. BMI, BMI z-scores, blood lipids, renal function and BP in each group were evaluated during the study period. RESULTS: BMI 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. CONCLUSIONS: The 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.