Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2009, vol. 18, nr 6, November-December, p. 559–565

Publication type: original article

Language: English

Association of Soluble IL−4R Serum Levels and IL−4Rα Chain Gene Polymorphisms

Stężenie rozpuszczalnej formy receptora IL−4 w odniesieniu do polimorfizmu genu IL−4Rα

Hanna Danielewicz1,, Magdalena Hurkacz2,, Andrzej Boznański1,, Annawiela−hojeńsk Annawiela−Hojeńska2,, Anna Chamerska−Drabik1,

1 First Department and Clinic of Pediatrics, Allergology, and Cardiology, Wroclaw Medical University, Poland

2 Chair and Department of Clinical Pharmacology, Wroclaw Medical University, Poland

Abstract

Background. The IL−4 receptor plays a key role in IL−4 signal transmission, immunoglobulin isotype switching, and Th2 differentiation. These processes are directly associated in the response to allergens and chronic allergic inflammation. Soluble sIL−4R is part of the homeostatic mechanism for IL−4. With an appropriate sIL−4R/IL−4 ratio, it can act as an IL−4 inhibitor; this mechanism was implemented in innovative asthma therapy. Polymorphisms in the IL−4Rα gene, among others C−3223T and I50V, have been reported to be associated with atopy. They may potentially affect the function of the gene and the decoded protein.
Objectives. The aim of the study was to analyze the serum levels of sIL−4R in children and adults in relation to atopy and C−3223T and I50V genotype.
Material and Methods. Serum levels of sIL−4R were determined by ELISA in children and adults (n = 106) previously genotyped for both polymorphisms.
Results. The study found statistically significant differences in the level of sIL−4R in relation to genotype in the group of children (p < 0.05, Whitney−Mann U test). The atopic children had lower levels of sIL−4R than controls, although the results were not statistically significant. In the adults there were no statistical significant differences in serum sIL−4R levels.
Conclusion. The findings point to a potentially significant role of C−3223T and possibly of I50V in the negative regulation of the IL−4 pathway.

Streszczenie

Wprowadzenie. Receptor dla IL−4 pełni kluczową rolę w przekazywaniu sygnału związanego z IL−4, a tym samym w procesie przełączania klas immunoglobulin oraz przekierowaniu odpowiedzi układu immunologicznego w kierunku Th2. Procesy te są związane bezpośrednio zarówno z reakcją organizmu na alergeny, jak i utrzymywaniem się stanu przewlekłego zapalenia alergicznego. Rozpuszczalna forma receptora dla IL−4 (sIL−4R) jest elementem układu homeostatycznego dla IL−4. Przy odpowiednim stosunku stężeń obu czynników może pełnić funkcję hamującą działanie IL−4, który to mechanizm wykorzystano w innowacyjnych formach terapii astmy. Polimorfizmy w regionie genu dla łańcucha alfa receptora IL−4, między innymi C−3223T i I50V, zostały opisane jako czynniki związane z występowaniem atopii. Potencjalnie mogą wpływać na funkcje genu oraz kodowanego białka.
Cel pracy. Analiza surowiczych stężeń sIL−4R u dzieci oraz osób dorosłych w odniesieniu do cech atopii i wymienionych genotypów.
Materiał i metody. Surowicze stężenia sIL−4R oznaczono z wykorzystaniem techniki ELISA w grupie dzieci i osób dorosłych (n = 106), u których pierwotnie oznaczono genotyp dla obu polimorfizmów.
Wyniki. Wykazano różnice w stężeniach sIL−4R w grupie dzieci w odniesieniu do genotypów (p < 0,05, Whitney−Mann U rank test). U dzieci z atopią obserwowano mniejsze stężenia sIL−4R w porównaniu z grupą kontrolną, różnice jednak były nieistotne statystycznie. W grupie dorosłych nie wykazano również statystycznie istotnych różnic w stężeniach sIL−4R.
Wnioski. Uzyskane wyniki potencjalnie wskazują na znaczącą rolę C−3223T oraz I50 V w regulacji immunologicznej związanej z IL−4.

Key words

sIL−4R, IL−4Rα gene promoter, genetic polymorphism

Słowa kluczowe

sIL−4R, promotor genu IL−4Rα, polimorfizm genetyczny

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