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内皮型一氧化氮合酶单倍型对高血压和2型糖尿病患者血浆一氧化氮产物浓度的影响。

Influence of eNOS haplotypes on the plasma nitric oxide products concentrations in hypertensive and type 2 diabetes mellitus patients.

作者信息

Sandrim Valeria C, de Syllos Roger W C, Lisboa Hugo R K, Tres Glaucia S, Tanus-Santos Jose E

机构信息

Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil.

出版信息

Nitric Oxide. 2007 May;16(3):348-55. doi: 10.1016/j.niox.2006.12.007. Epub 2007 Jan 12.

DOI:10.1016/j.niox.2006.12.007
PMID:17306574
Abstract

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 (NO(x)), 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. NO(x) concentrations were assessed using a chemiluminescence assay. No differences were found in genotype/allele distribution among groups. Genotypes were not associated with NO(x) 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 microM, respectively) than with low (35+/-7 and 34+/-7 microM, respectively) NO(x) 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 NO(x) levels among hypertensives. Conversely, the haplotype increasing the risk of developing hypertension is associated with lower NO(x) levels in hypertensives.

摘要

内皮型一氧化氮合酶(eNOS)单倍型与有或无2型糖尿病(T2DM)患者的高血压(HT)相关。我们评估了eNOS基因型/单倍型与亚硝酸盐/硝酸盐(NO(x))血浆浓度的关联,NO(x)是HT、T2DM和T2DM + HT患者体内一氧化氮的产物。我们研究了98名对照者、68名HT患者、66名T2DM患者和86名T2DM + HT患者中eNOS基因在启动子区域(T - 786C)、外显子7(Glu298Asp)和内含子4(b/a)的多态性。使用化学发光分析法评估NO(x)浓度。各群体间基因型/等位基因分布未发现差异。基因型与NO(x)浓度无关。“C - Glu - b”单倍型在对照组中比在HT/T2DM + HT组中更常见(分别为21%对9/5%,P<0.006)。在NO(x)浓度高的受试者中(分别为82±38和90±33微摩尔),该单倍型在HT和T2DM + HT组中比浓度低的受试者中(分别为35±7和34±7微摩尔)更常见。相反,“C - Asp - b”单倍型在HT/T2DM + HT组中比健康组更常见(分别为21/21%对10%,P<0.006)。与患高血压风险较低相关的单倍型在高血压患者中也与较高的NO(x)水平相关。相反,增加患高血压风险的单倍型与高血压患者较低的NO(x)水平相关。

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