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

2011, vol. 20, nr 4, July-August, p. 413–421

Publication type: original article

Language: English

The Effect of CD14 and TLR4 Gene Polymorphisms on the Occurrence of Atopic and Non-Atopic Asth

Wpływ polimorfizmu genu CD14 i TLR4 na występowanie atopowej i nieatopowej astmy oskrzelowej

Tomasz Zaborowski1,, Kamila Wojas-Krawczyk1,, Paweł Krawczyk1,, Olga Jankowska1,, Jan Siwiec1,, Tomasz Kucharczyk1,2,, Maciej Grzybek3,, Janusz Milanowski1,4,

1 Department of Pneumonology, Oncology and Allergology, Medical University, Lublin, Poland

2 Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland

3 Faculty of Biology and Animal Breeding, University of Life Science, Lublin, Poland

4 Institute of Agriculture Medicine, Lublin, Poland

Abstract

Background. A significant increase in the incidence of asthma which has been observed in recent years leads many researchers to the opinion that it is not caused only by hereditary factors but also by exposure to external factors. The fact that environmental changes cause asthma should not exclude other causes though, especially in atopic, genetically-predisposed individuals. Evidence of this phenomenon is the protective effect of lipopolysaccharide on the incidence of atopic asthma in carriers of certain polymorphic variations of LPS receptor genes: TLR4 and CD14.
Objectives. The aim of this study was to determine the genetic predisposition to the occurrence of asthma, depending on the variability of the endotoxin receptor gene.
Material and Methods. The study included a group of 106 individuals diagnosed with asthma. The control group numbered 159 healthy individuals. Using the RFLP-PCR technique, polymorphism –159C < T of the CD14 gene and 1187A < G of the TLR4 gene were identified. In addition, the number of eosinophiles in peripheral blood and the total concentration of IgE in serum were determined in the group of individuals with asthma.
Results. The TT genotype in position 159 of CD14 and the AA genotype in position 1187 of TLR4 are present significantly less frequently in atopic asthma and are associated with a lower concentration of IgE in blood serum in individuals with asthma. CC homozygotes in the CD14 gene and AG heterozygotes in the TLR4 gene correspond to a higher risk of occurrence of atopic asthma, while the TT genotype of the CD14 gene and AA of the TLR4 gene are connected with a higher risk of non-atopic asthma. Conclusion. Atopic and non-atopic asthma differ in etiology at the molecular level. Exposure to endotoxin in patients with the characteristic polymorphisms of genes for LPS receptors may have a protective effect on the development of atopic asthma.

Streszczenie

Wprowadzenie. Znaczące zwiększenie zachorowań na astmę oskrzelową obserwowane w ostatnich dekadach sprawia, że większość badaczy przyczyny tego zjawiska dopatruje się bardziej po stronie zmieniającego się narażenia na czynniki zewnętrzne, niż w predyspozycjach dziedzicznych. Nie można jednak wykluczyć, że zmiany środowiska wywołują astmę oskrzelową, zwłaszcza atopową u osób predysponowanych genetycznie. Dowodem na to ma być protekcyjny wpływ lipopolisacharydu na częstość występowania astmy atopowej u nosicieli pewnych polimorficznych odmian genów receptorów LPS: TLR4 i CD14.
Cel pracy. Określenie genetycznej predyspozycji do wystąpienia astmy oskrzelowej w zależności od zmienności genów receptorów dla endotoksyny.
Materiał i metody. Badaniem objęto grupę 106 chorych z rozpoznaną astmą oskrzelową. Grupę kontrolną stanowiło 159 osób zdrowych. Z użyciem metody PCR RFLP oznaczono polimorfizm –159C < T genu CD14 oraz polimorfizm 1187A < G genu TLR4. W grupie osób chorych na astmę oskrzelową oznaczono ponadto liczbę eozynofili we krwi obwodowej oraz stężenie IgE całkowitego w surowicy krwi.
Wyniki. Genotyp TT w pozycji 159 genu CD14 oraz genotyp AA w pozycji 1187 genu TLR4 wiąże się z istotnie rzadszym występowaniem atopowej astmy oskrzelowej i mniejszym stężeniem IgE całkowitego w surowicy krwi osób chorych na astmę oskrzelową. Homozygoty CC w genie CD14 oraz heterozygoty AG w genie TLR4 charakteryzują się większym ryzykiem wystąpienia astmy atopowej. Genotyp TT genu CD14 i AA genu TLR4 sprzyja natomiast powstawaniu astmy nieatopowej.
Wnioski. Atopowa i nieatopowa astma oskrzelowa różnią się etiologią na poziomie molekularnym. Ekspozycja na endotoksynę u chorych z odpowiednimi polimorfizmami genów receptorów dla LPS może wywierać efekt protekcyjny na rozwój atopowej astmy oskrzelowej.

Key words

asthma, polymorphism, TLR4 gene, CD14 gene, lipopolysaccharide

Słowa kluczowe

astma, polimorfizm, TLR4, CD14, lipopolisacharyd

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