Hoffmann I S, Tavares-Mordwinkin R, Castejon A M, Alfieri A B, Cubeddu L X
Center for the Detection and Treatment of Silent Risk Factors for Cardiovascular and Metabolic Disease, Division of Clinical Pharmacology Unit, School of Pharmacy, Central University of Venezuela.
J Hum Hypertens. 2005 Mar;19(3):233-40. doi: 10.1038/sj.jhh.1001801.
Mutations in the endothelial nitric oxide synthase (eNOS) gene may be associated with abnormal nitric oxide (NO) production and cardiovascular diseases. In this study, we investigated the prevalence of two eNOS polymorphisms, the Glu298Asp variant on exon 7, and the 4a/b variable number of tandem repeats (VNTR) on intron 4, and their association with blood pressure (BP), NO production, salt sensitivity and cardiovascular risk factors in healthy Venezuelans. The prevalence of both polymorphisms in Venezuelans was comparable to that described for Caucasians, but significantly different from that known for African-Americans and Japanese. The 4a/b genotype was associated with reduced levels of NO metabolites (25% decrease), larger BP lowering in response to salt restriction (9.0 vs 4.8 mmHg, P<0.05), greater prevalence of salt sensitivity (39% in 4a/b and 27% in 4b/b; P<0.05) and with higher LDL-cholesterol levels. The Glu298T polymorphism did not affect NO production, nor it was associated with salt sensitivity. Glu298Asp polymorphism was positively associated with higher weight, triglycerides and LDL-cholesterol. Neither polymorphism was associated with changes in fasting or postload serum glucose, BP, obesity and albuminuria. In conclusion, the prevalence of eNOS polymorphisms is strongly determined by ethnic factors. The 4a/b gene polymorphism could be a genetic susceptibility factor for the BP response to salt intake and for the genetic control of NO production. The reduced NO production in subjects with the 4a/b genotype may be responsible for the increased sensitivity of their BP to salt.
内皮型一氧化氮合酶（eNOS）基因突变可能与一氧化氮（NO）生成异常及心血管疾病相关。在本研究中，我们调查了两种eNOS基因多态性的流行情况，即第7外显子上的Glu298Asp变异以及第4内含子上的4a/b可变串联重复序列（VNTR），并研究了它们与健康委内瑞拉人血压（BP）、NO生成、盐敏感性及心血管危险因素之间的关系。委内瑞拉人这两种多态性的流行情况与高加索人描述的相当，但与非裔美国人和日本人已知的情况显著不同。4a/b基因型与NO代谢产物水平降低（降低25%）、盐限制时更大的血压降低幅度（9.0 vs 4.8 mmHg，P<0.05）、更高的盐敏感性患病率（4a/b为39%，4b/b为27%；P<0.05）以及更高的低密度脂蛋白胆固醇水平相关。Glu298T多态性不影响NO生成，也与盐敏感性无关。Glu298Asp多态性与更高的体重、甘油三酯和低密度脂蛋白胆固醇呈正相关。两种多态性均与空腹或负荷后血清葡萄糖、血压、肥胖和蛋白尿的变化无关。总之，eNOS基因多态性的流行情况受种族因素强烈影响。4a/b基因多态性可能是血压对盐摄入反应及NO生成遗传控制的遗传易感性因素。4a/b基因型受试者中NO生成减少可能是其血压对盐敏感性增加的原因。
