P158EDN1 Lys198Asn is associated with microvascular angina or cardiac syndrome X in women

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In women with a diagnosis of ischemic heart disease (IHD) besides atherosclerosis of coronary artery unchanged coronary vessels are revealed by angiography. The one reason of smooth coronary artery is microvascular angina or "cardiac syndrome X". Leading role in the development of this disease is belongs to endothelial dysfunction, which may be because of genetic polymorphism of the endothelin-1 and NO synthase.


To study the distribution of allele and genotype frequencies of polymorphisms Lys198Asn gene endothelin-1 and 4a/4b gene ecNOS in women of young and middle age with IHD compared with women of similar age without clinical manifestations of coronary artery disease and family history of cardiovascular disease.

Materials and Methods

222 women were included. 115 women had coronary atherosclerosis (stenosis of coronary artery more than 70%) (average age 52,7 ± 0,5 years), 36 women had diagnosis "cardiac syndrome X" (mean age 55.6 ± 1,0 years) and 71 women were without clinical evidence of coronary heart disease (average age 51,3 ± 1,0 years). Detection of polymorphisms Lys198Asn EDN1 and 4a/4b ecNOS was conducted by PCR followed by restriction analysis.


In group of women with coronary atherosclerosis was found the following distribution of genotypes - 54%, 42% and 4% for the 4b4b, and 4a4a, a group of women with "cardiac syndrome X"- 58%, 36% and 6% for the 4b4b, 4a4b and 4a4a, and a group of women with no history of coronary heart disease - 66%, 32% and 2% for genotypes 4b4b, 4a4b and 4a4a, respectively (p=0.06). Thus, for ecNOS 4a4b polymorphism statistically significant differences were not found.


In the analysis of gene EDN1 genotype distribution the following data were found. In group of women with coronary atherosclerosis - 60%, 31% and 9%, with cardiac syndrome X - 3%, 89% and 8% in women without coronary heart disease - 37%, 62% and 1% for genotypes LysLys, LysAsn and AsnAsn, respectively were revealed. It was found statistically significant increase in frequency of mutant allele Asn gene EDN1 (in hetero-and homozygous state) in women with cardiac syndrome X in comparison with a group of women with coronary atherosclerosis (p = 0.0003) and a group of healthy individuals ( p = 0.00001).


The polymorphic markers 4a/4b ecNOS is not involved in the development of coronary heart disease among women of young and middle age, but it is quite obvious that the polymorphic marker Lys198Asn EDN1 may be associated with the development of women "cardiac syndrome X".

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