Endothelial nitric oxide synthase (eNOS) haplotypes are associated with hypertension (HT) in patients with or without type 2 diabetes mellitus (T2DM). We evaluated the association of eNOS genotypes/haplotypes with the plasma concentrations of nitrite/nitrate (NOx), which are products of nitric oxide in HT, T2DM, and T2DM+HT patients. We. studied eNOS polymorphisms in the promoter region (T-786C), in exon 7 (Glu298Asp), and in intron 4 (b/a) in 98 controls, 68 patients with HT, 66 patients with T2DM, and 86 patients with T2DM+HT. NOx concentrations were assessed using a chemiluminescence assay. No differences were found in genotype/allele distribution among groups. Genotypes were not associated with NOx concentrations. The 'C-Glu-b' haplotype was more common in controls than in HT/T2DM + HT groups (21% versus 9/5%, respectively, P < 0.006). This haplotype was more common in HT and T2DM + HT groups among subjects with high (82 +/- 38 and 90 +/- 33 mu M, respectively) than with low (35 +/- 7 and 34 7 mu M, respectively) NOx concentrations. Conversely, the 'C-Asp-b' haplotype was more common in HT/T2DM+HT groups than healthy (21/21% versus 10%, respectively, P < 0.006). The haplotype associated with lower risk of developing hypertension is also associated with higher NOx levels among hypertensives. Conversely, the haplotype increasing the risk of developing hypertension is associated with lower NOx levels in hypertensives. (c) 2007 Elsevier Inc. All rights reserved.163348355