Endothelial nitric oxide synthase polymorphisms associated with abnormal nitric oxide production are not over-represented in children with Down syndrome.

Objective: Down syndrome patients are at increased risk for developing pulmonary hypertension (PHTN). Nitric oxide (NO) is an important factor for pulmonary vasoreactivity. Various endothelial nitric oxide synthase (eNOS) polymorphisms have been shown to affect NO. The goal of this study was to determine whether there was a difference in prevalence of eNOS polymorphisms between Down syndrome patients vs. non-Down syndrome patients.

Methods: Down syndrome patients were recruited as well as non-Down syndrome patients. Gene polymorphisms for eNOS-3 (GG, GT, TT), eNOS-4 (bb, ba, aa), and eNOS-P (TT, TC, CC) were determined. Three forms of the 3 genes were compared in cross-tabulation tables with Down syndrome patients vs. non-Down syndrome patients and Down syndrome patients with heart defects vs. those without defects. Association was tested with chi-square and significance was set at P < or = .05.

Results: Fifty-one Down syndrome patients and 411 controls were studied. Twenty-one Down syndrome patients had heart defects and 6 of these patients had documented PHTN. There was no difference in gender between Down syndrome patients (males 56.9%) and controls (males 50.4%), P = .38. Prevalence of eNOS polymorphisms between Down syndrome patients and controls was not different for the genes (eNOS-3, P = .94; eNOS-4, P = .40; eNOS-P, P = .18). There was no difference in gene polymorphisms between Down syndrome patients with heart defects vs. those without defects (eNOS-3, P = .19; eNOS-4, P = .29; eNOS-P, P = .99).

Conclusion: Prevalence of various eNOS polymorphisms between Down syndrome patients and controls was not different. Other polymorphisms that are associated with PHTN should be studied to determine whether they may be the cause of the increased risk of PHTN in Down syndrome patients.