Genetic polymorphisms of angiotensin system genes in congenital diaphragmatic hernia associated with persistent pulmonary hypertension.

BACKGROUND/PURPOSE: The renin-angiotensin system plays an important role in pulmonary artery remodelling. Several polymorphisms of genes encoding for components of the renin angiotensin system such as the angiotensin converting enzyme (ACE), the angiotensinogen (AGT) gene, and the angiotensin II type 1 receptor (ATIR) have been associated with the development of pulmonary hypertension. The aim of this study was to investigate the ACE I/D genotype, the M235 T polymorphism of the AGT gene and the A1166 C polymorphism of AT1R in the lungs of congenital diaphragmatic hernia (CDH) complicated by persistent pulmonary hypertension (PPH) in the newborn.

METHODS: Genomic DNA was extracted from archival paraffin-embedded lung tissue from 13 newborns with CDH complicated by PPH and from 9 controls. Genotyping for the I/D-ACE, the M235 T-AGT, and the A1166 C-ATIR gene polymorphisms were determined by a polymerase chain reaction-based method with appropriate restriction digest when required.

RESULTS: In controls, ACE genotype distribution of DD, ID, and II was 11%, 33%, and 55%, respectively, whereas in CDH it was 70%, 15%, and 15%, respectively. The ACE-DD genotype was significantly higher in CDH compared with controls (P <.05). In CDH samples, the prevalence of AGT-MM genotype was lower (8% v. 33%; P <.05), whereas the AGT-TT genotype was higher (61% v. 22%; P <.05) compared with controls. There were no differences in allele frequencies of AT1R between CDH patients and controls.

CONCLUSIONS: These data suggest that D allele of the ACE gene insertion/deletion polymorphism and angiotensinogen M235 T polymorphism may be associated with PPH in newborns with congenital diaphragmatic hernia.