Effect of ecNOS polymorphisms and coronary artery disease upon exhaled nitric oxide

被引:27
作者
Thomas, PS [1 ]
Bruce, C
Birkhead, A
Wang, XL
机构
[1] Prince Wales Hosp, Dept Resp, Randwick, NSW 2031, Australia
[2] Prince Wales Hosp, Dept Cardiovasc Genet, Randwick, NSW 2031, Australia
[3] Univ New S Wales, Fac Med, Sydney, NSW, Australia
[4] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 2002年 / 80卷 / 03期
基金
英国医学研究理事会;
关键词
nitric oxide; nitric oxide synthase; coronary disease; genes;
D O I
10.1007/s00109-001-0301-7
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Exhaled nitric oxide (eNO) is thought to arise principally from the airway epithelium. NO regulates smooth muscle tone, and abnormal activity of NO synthase has been implicated in coronary artery disease (CAD). Polymorphisms of endothelial constitutive NO synthase (ecNOS) may affect NO generation and be associated with CAD. It was hypothesised that a polymorphism, such as the ecNOS intron 4 polymorphism (ecNOS4a), affects the levels of eNO via airway epithelial NOS. eNO levels were measured in 53 patients with ischaemic chest pain who had previously been genotyped for ecNOS polymorphisms, with sample enrichment for the ecNOS4a allele. Subjects were also assessed for two other ecNOS polymorphisms (T-786C substitution in the promoter region, and G5557T in exon 7), variably associated with vascular disease. Those homozygous for the 'a' allele (ecNOS4a/a) had a lower mean eNO (9.0 ppb) than those who were heterozygous (ecNOS4a/b, 13.6 ppb), who in turn had a lower level than those homozygous for the wild-type ecNOS4b/b (16.1 ppb). No association of eNO levels was found with the other polymorphisms. Levels of eNO remained significantly lower in the ecNOSa/a subjects than in the ecNOSa/b and ecNOSb/b subjects, even when controlled for angiographic CAD, and smoking habit. In addition, all subjects with CAD had a significantly lower mean eNO (12.1 ppb) than subjects without angiographic CAD (19.9 ppb). In this selected population low levels of eNO were thus associated with presence of the ecNOS4a allele and also with CAD.
引用
收藏
页码:181 / 186
页数:6
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