Genetic evidence that nitric oxide modulates homocysteine -: The NOS3 894TT genotype is a risk factor for hyperhomocystenemia
Genetic evidence that nitric oxide modulates homocysteine -: The NOS3 894TT genotype is a risk factor for hyperhomocystenemia
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DOI：
10.1161/01.atv.0000071348.70527.f4
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发表时间：
2003-06-01
影响因子：
8.7
通讯作者：
Whitehead, AS
中科院分区：
文献类型：
--
作者：
Brown, KS;Kluijtmans, LAJ;Whitehead, AS
轻度高同型半胱氨酸血症是心血管疾病的独立、分级危险因素。高同型半胱氨酸血症的遗传决定因素包括几种叶酸/同型半胱氨酸代谢酶的功能多态性。一氧化氮也可以调节血浆同型半胱氨酸（tHcy）的浓度，无论是通过直接抑制甲硫氨酸合酶或通过间接影响叶酸catalin.Methods和结果的假设，即内皮型一氧化氮合酶（NOS 3）G894 T多态性是一个遗传决定因素的tHcy浓度进行了测试，在2个独立的健康成人人群。在这两个人群中，NOS 3基因型与低叶酸非吸烟者的tHcy浓度显著相关（P = 0.03）。构建模型以调整tHcy浓度的已知决定因素，并测试来自每个人群的非吸烟者中NOS 3基因型与这些决定因素之间的相互作用。校正后，NOS 3基因型仍是tHcy浓度的显著决定因素。NOS 3基因型与血清叶酸之间的交互作用在两个人群中均显著，NOS 3基因型与MTHFR C677 T基因型的交互作用在较大人群中显著。这些数据表明，NOS 3 894 TT基因型是低血清叶酸水平的健康非吸烟成人中tHcy升高的危险因素，并支持一氧化氮通过影响叶酸调节同型半胱氨酸的假设猫
Objective-Mild hyperhomocystenemia is an independent, graded risk factor for cardiovascular disease. Genetic determinants of hyperhomocystenemia include functional polymorphisms in several folate/homocysteine metabolic enzymes. Nitric oxide may also modulate plasma homocysteine (tHcy) concentrations, either by direct inhibition of methionine synthase or via an indirect effect on folate catabolism.Methods and Results-The hypothesis that the endothelial nitric oxide synthase (NOS3) G894T polymorphism is a genetic determinant of tHcy concentrations was tested in 2 independent healthy adult populations. In both populations, NOS3 genotype was significantly associated with tHcy concentrations in nonsmokers with low folate (P = 0.03 for each). Models were constructed to adjust for known determinants of tHcy concentrations and test for interactions between NOS3 genotype and these determinants in nonsmokers from each population. NOS3 genotype remained a significant determinant of tHcy concentrations after adjustment. Interactions between NOS3 genotype and serum folate were significant in both populations, and the interaction between NOS3 genotype and MTHFR C677T genotype was significant in the larger population.Conclusions-These data indicate that the NOS3 894TT genotype is a risk factor for elevated tHcy in healthy nonsmoking adults with low serum folate and supports the hypothesis that nitric oxide modulates homocysteine through an effect on folate catabolism.