Boston - American Association for Thoracic Surgery

AMERICAN ASSOCIATION FOR THORACIC SURGERY23. Endothelial Nitric Oxide Synthase Gene Polymorphism andPulmonary Hypertension in Children with Congenital HeartDiseasesTsvetomir S. Loukanov, 1 Christian Sebening, 1 Nina Hoss, 2 Pencho Tonchev, 2Matthias Karck, Matthias Gorenflo1. Cardiac Surgery, University of Heidelberg, Heidelberg, Germany; 2. PediatricCardiology, University of Heidelberg, Heidelberg, GermanyInvited Discussant: Paul M. KirshbomOBJECTIVE: The operative correction of the congenital heart diseases in childrenwith left-right shunt is often associated with post operative pulmonary hypertension(PH). This paper discusses the correlation between the Glu298Asp polymorphismof the gene eNOS and PH in children with congenital heart diseases.MONDAYAfternoonMETHODS: The study group includes 80 children (m = 41; f = 39) on the averageage 3.8 [0.1–36.2] years (median [range]) with congenital heart diseases and 136children as a control group. Patients presented with significant left-to- right shunt(Qp/Qs of 2.8 [1.4–7.5]). Forty out of 80 patients showed PH with mean pressure(PAP) of 30 [13- 82] mmHg prior to the intra-cardiac repair. Fifteen out of 31 operatedpatients were found to have postoperative persistent PH.RESULTS: The Glu298Asp polymorphism was identified using polymerase-chainreaction (PCR) and Restriction Fragment Length Polymorphism (RFLP). In bothgroups, the control group and the group of 80 patients, the genotypes distributioncorresponded to the Hardy-Weinberg Equilibrium (HWE) – Chi2 = 0.96 and Chi2= 0.25. The gene frequency for Glu298Glu, Glu298Asp and Asp298Asp was notdifferent in control group compared with the group of patients (Chi-square = 0.79;2 degree of freedom; p = 0.37477). The Armitage trend test showed however aclearly significant result (53.3% vs 25.0%; p = 0.03799) for the correlation of e-NOSpolymorphism and post-operative PH. Significant association between the postoperativePH and the allele frequencies of the Glu298Asp was determined with Fischer’sExact Test (p = 0.0481, one-sided).CONCLUSION: The investigation of the polymorphism concerning postoperativePH after intra-cardiac surgery shows that Asp- carrier patients have morefrequently persistent PH. The Glu-Asp polymorphism of the gene e-NOS would beindicated as genetic marker for predisposition for the development of persistentpulmonary hypertension.111