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A new erythropoietin gene polymorphism is associated with severe hypertension, endorgan damage and vascular events
Ein neuer Erythropoietin-Gen-Polymorphismus ist assoziiert mit schwerer Hypertonie, Endorganschäden und vaskulären Ereignissen
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Veröffentlicht: | 10. August 2005 |
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Introduction: The pathomechanism of essential hypertension is still not clear. Additionally to aspects of life-style genetic disorders may play a role for the severeness and prognosis of the disease. The erythropoietin gene went to major interest since its interaction with vasoactive substances such as endothelin and angiotensin II became aware. Further investigations on the the hypoxia responsive element in patients with erythrocytosis elucidated several polymorphisms in this regulatory part of the EPO-gene.
Methods: In 400 hypertensive patients and 150 age and gender matched normotensive controls the hypoxia responsive region was analyzed after detection of a new Thymine-Guanine-polymorphism at position 3541 by DNA-sequencing. Hypertension was defined as BP > 135/85 mmHg in ABDM (24-h-bloodpressure measurement) or normotension under antihypertensive treatment of minimum1 drug.
Results: The highest incidence overall demonstrated the TG-genotype (60 % of the normotensives; 55,4 % of the hypertensives). Hypertensives showed 28,2 % TT homocygote formation compared to 22,0 of matched controls. TT homocygote individuals demondstrated more often a severe hypertension (34,4 %) and hypertensive especially renal endorgan damage (endstage renal failure 60,0; atherosclerosis 35,3; vascular events 32,2 %, coronary artery disease 38,0 %) than TG or GG alteration.
Conclusions: The detected erythropoietin gene polymorphism revealed a different vascular risk for the 3 genotypes. Homozygote TT contributes to a higher prevalence of severe hypertension with serious forms of endorgan damage especially endstage renal failure. Although the regulatory role of the genetic alteration has to be investigated the polymorphism at position 3541 could serve as a possibility to differentiate high risk subgroups in the heterogenous population of hypertensive patients.