TY - JOUR
T1 - Renin-angiotensin-aldosterone genotype influences ventricular remodeling in infants with single ventricle
AU - Mital, Seema
AU - Chung, Wendy K.
AU - Colan, Steven D.
AU - Sleeper, Lynn A.
AU - Manlhiot, Cedric
AU - Arrington, Cammon B.
AU - Cnota, James F.
AU - Graham, Eric M.
AU - Mitchell, Michael E.
AU - Goldmuntz, Elizabeth
AU - Li, Jennifer S.
AU - Levine, Jami C.
AU - Lee, Teresa M.
AU - Margossian, Renee
AU - Hsu, Daphne T.
PY - 2011/5/31
Y1 - 2011/5/31
N2 - Background-: We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function, and response to enalapril in infants with single ventricle. Methods and results-: Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with renin-angiotensin- aldosterone system upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate, and response to enalapril were compared between patients with 2 homozygous risk genotypes (high risk), and those with <2 homozygous risk genotypes (low risk) at 2 time points: before the superior cavopulmonary connection (pre-SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: Thirty-eight were high risk, and 116 were low risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and estimated glomerular filtration rate increased after SCPC in the low-risk (P<0.05), but not the high-risk group. These responses were independent of enalapril treatment. Weight and height z-scores were lower at baseline, and height remained lower in the high-risk group at 14 months, especially in those receiving enalapril (P<0.05). Conclusions-: Renin-angiotensin-aldosterone system-upregulation genotypes were associated with failure of reverse remodeling after SCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. Renin-angiotensin-aldosterone system genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume-unloading surgery. Follow-up is warranted to assess long-term impact.
AB - Background-: We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function, and response to enalapril in infants with single ventricle. Methods and results-: Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with renin-angiotensin- aldosterone system upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate, and response to enalapril were compared between patients with 2 homozygous risk genotypes (high risk), and those with <2 homozygous risk genotypes (low risk) at 2 time points: before the superior cavopulmonary connection (pre-SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: Thirty-eight were high risk, and 116 were low risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and estimated glomerular filtration rate increased after SCPC in the low-risk (P<0.05), but not the high-risk group. These responses were independent of enalapril treatment. Weight and height z-scores were lower at baseline, and height remained lower in the high-risk group at 14 months, especially in those receiving enalapril (P<0.05). Conclusions-: Renin-angiotensin-aldosterone system-upregulation genotypes were associated with failure of reverse remodeling after SCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. Renin-angiotensin-aldosterone system genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume-unloading surgery. Follow-up is warranted to assess long-term impact.
KW - angiotensin-converting enzyme inhibitors
KW - congenital heart disease
KW - genetic association analysis
KW - heart surgery
KW - hypertrophy
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U2 - 10.1161/CIRCULATIONAHA.110.004341
DO - 10.1161/CIRCULATIONAHA.110.004341
M3 - Article
C2 - 21576655
AN - SCOPUS:79958100222
SN - 0009-7322
VL - 123
SP - 2353
EP - 2362
JO - Circulation
JF - Circulation
IS - 21
ER -