Tsukada T, Yokoyama K, Arai T, Takemoto F, Hara S, Yamada A, Kawaguchi Y, Hosoya T, Igari J
Department of Clinical Chemistry, Toranomon Hospital, Tokyo, 105, Japan.
Biochem Biophys Res Commun. 1998 Apr 7;245(1):190-3. doi: 10.1006/bbrc.1998.8267.
Nitric oxide (NO) synthesized by the vascular endothelium regulates mammalian blood vessels and other systems in humans. Recently, an endothelial nitric oxide synthase (ecNOS) gene polymorphism, the 27-bp repeat in intron 4 (ecNOS4), was reported to be related to the pathogenesis of coronary heart disease and terminal renal failure. We analyzed this polymorphism in a group of 413 healthy subjects, and measured their plasma nitrite and nitrate (NOx) levels. The frequency of the b allele was 89.8% , and the frequency of the a allele was 10.2%. The frequency of ecNOS4 b/b, ecNOS4 b/a, and ecNOS4 a/a in the healthy subjects in this study was 0.814 (n=336), 0.169 (n=70) and 0.017 (n=7), respectively. Using this polymorphism as a DNA marker, we found a strong association between the alleles of the ecNOS gene polymorphism and the plasma NOx levels. The basal NO metabolite levels were 28.8 micromol/L in subjects with ecNOS4 a/a, 31.4 micromol/L in those with ecNOS4 b/a, and 35.5 micromol/L in those with ecNOS4 b/b. The mean plasma NOx level of the subjects who were homozygous for the a allele was nearly 20% lower than in the subjects with the b allele. The plasma NOx level of the subjects with the a allele was 31.2+/-2.00 micromol/L, and significantly lower than the 35.5+/-0.93 micromol/L in those without the a allele (P <0.05). The results of this study indicate that the ecNOS4 gene locus may be responsible for variations in the genetic control of plasma NOx and that analysis of ecNOS4 gene polymorphism may be a useful tool for studying the relation between NO and diseases.
血管内皮合成的一氧化氮（NO）调节人体的哺乳动物血管及其他系统。最近，有报道称内皮型一氧化氮合酶（ecNOS）基因多态性，即内含子4中的27bp重复序列（ecNOS4）与冠心病和终末期肾衰竭的发病机制有关。我们对413名健康受试者进行了该多态性分析，并测量了他们血浆中亚硝酸盐和硝酸盐（NOx）的水平。b等位基因频率为89.8%，a等位基因频率为10.2%。本研究中健康受试者ecNOS4 b/b、ecNOS4 b/a和ecNOS4 a/a的频率分别为0.814（n = 336）、0.169（n = 70）和0.017（n = 7）。以这种多态性作为DNA标记，我们发现ecNOS基因多态性的等位基因与血浆NOx水平之间存在强关联。ecNOS4 a/a受试者的基础NO代谢产物水平为28.8微摩尔/升，ecNOS4 b/a受试者为31.4微摩尔/升，ecNOS4 b/b受试者为35.5微摩尔/升。a等位基因纯合受试者的平均血浆NOx水平比b等位基因受试者低近20%。有a等位基因受试者的血浆NOx水平为31.2±2.00微摩尔/升，显著低于无a等位基因受试者的35.5±0.93微摩尔/升（P<0.05）。本研究结果表明，ecNOS4基因位点可能是血浆NOx遗传控制变异的原因，ecNOS4基因多态性分析可能是研究NO与疾病关系的有用工具。
