Impact of endothelin-1 Lys198Asn polymorphism on coronary artery disease and endorgan damage in hypertensives

OBJECTIVE: Endothelin is the most potent endogenous vasoconstrictor and is involved in several vascular disorders such as arterial hypertension. Its intense interaction with other vasoactive hormone systems revealed the consideration about the endothelin gene as an interesting candidate for influencing the development of essential hypertension and hypertensive endorgan damage. The purpose of this study was to investigate the role of endothelin-1 Lys198Asn polymorphism in patients with severe arterial hypertension as well as associated endorgan damages. METHODS: In 400 hypertensive patients and 150 normotensive controls we examined the endothelin-1 Lys198Asn polymorphism by DNA sequencing and patients were divided according to their genotype (GG, GT, and TT). Moreover, the frequency of endothelin-1 Lys198Asn polymorphism was investigated with respect to the prevalence of several actual or historical endorgan damages (renal disorder, coronary artery disease, vascular events, vascular damage, and congestive heart failure) in hypertensive patients. RESULTS: Genotype distribution for endothelin-1 Lys198Asn polymorphism was 57.3% (GG), 41.3% (GT), and 1.43% (TT) in normotensive individuals; and in hypertensive individuals was 54.75% (GG), 43% (GT) and 2.25% (TT). Genotype distribution was unaffected in patients with severe hypertension, renal disorder, vascular events, vascular damage, and congestive heart failure. We, however, found a significant difference in hypertensive individuals with coronary artery disease and TT genotype (P=0.004). CONCLUSION: Homozygous TT carrier contributes to a higher prevalence of coronary artery disease, especially for three-vessel disease in hypertensive individuals. Thus, the polymorphism at position 198 could serve as a possibility to differentiate high-risk subgroups in the heterogeneous population of hypertensive patients.