BACKGROUND: Several studies suggest that the vasoactive peptide endothelin-1 (ET-1) could be involved in the pathophysiology of atopic asthma and allergic rhinitis. However, a possible involvement of polymorphisms of the corresponding gene in the origin of these conditions has so far not been subjected to a more comprehensive study. OBJECTIVE: This study investigates a possible association of two common polymorphisms in the ET-1 gene (TaqI in intron4 and BsiYI in position 138) with clinically manifested atopic diseases. The genetic linkage of these polymorphisms with the underlying phenotypes of asthma or parameters of atopy including total IgE level was examined, too. METHODS: The study included 456 subjects-270 Czech patients (Caucasians, Central Europe) with clinically manifested atopic diseases and 186 unrelated referent subjects with negative familial history of asthma/atopy. ET-1 genotypes were determined by PCR and restriction analysis by TaqI and BsiYI, respectively. RESULTS: No significant differences were found for the two polymorphisms between atopic patients and healthy subjects, or between subselected asthmatic patients and controls. However, the insertion exonic variant of ET-1 gene showed a significant association with signs of atopy, especially with total serum IgE levels (total IgE levels < or = 150 IU/ml turned out to be associated with DD genotypes, total IgE > 150 IU/ml with II and ID genotypes [OR = 3.76 (95% CI: 1.52-9.34), p = 0.003, Pc = 0.0061). CONCLUSIONS: These findings suggest that ET-1 may participate in the pathogenesis of high total serum IgE level in clinically manifested atopic diseases in our population.

Institute of Pathological Physiology Medical Faculty Masaryk University Brno Czech Republic

Montelukast decreases plasma endothelin-1 and serum eosinophil cationic protein levels in paediatric atopic asthma