Pilot Study of the Association of the DDAH2 2449G Polymorphism with Asymmetric Dimethylarginine and

Background: Genetic variability in the regulation of the nitric oxide (NO) pathway may influence hemodynamic changes in pediatric sepsis. We sought to determine whether functional polymorphisms in DDAH2, which metabolizes the NO synthase inhibitor asymmetric dimethylarginine (ADMA), are associated with susceptibility to sepsis, plasma ADMA, distinct hemodynamic states, and vasopressor requirements in pediatric septic shock. Methodology/Principal Findings: In a prospective study, blood and buccal swabs were obtained from 82 patients #18 years (29 with severe sepsis/septic shock plus 27 febrile and 26 healthy controls). Plasma ADMA was measured using tandem mass spectrometry. DDAH2 gene was partially sequenced to determine the 2871 6g/7g insertion/deletion and 2449G/C single nucleotide polymorphisms. Shock type (‘‘warm’ ’ versus ‘‘cold’’) was characterized by clinical assessment. The 2871 7g allele was more common in septic (17%) then febrile (4%) and healthy (8%) patients, though this was not significant after controlling for sex and race (p = 0.96). ADMA did not differ between 2871 6g/7g genotypes. While genotype frequencies also did not vary between groups for the 2449G/C SNP (p = 0.75), septic patients with at least one 2449G allele had lower ADMA (median, IQR 0.36, 0.30–0.41 mmol/L) than patients with the 2449CC genotype (0.55, 0.49– 0.64 mmol/L, p = 0.008) and exhibited a higher incidence of ‘‘cold’ ’ shock (45 % versus 0%, p = 0.01). However, after controlling for race, the association with shock type became non-significant (p = 0.32). Neither polymorphism wa