Abstract
Background: Experimental studies indicate that endogenous plasminogen activator inhibitor-1 (PAI-1, encoded by the gene SERPINE1) modulates the immune response to lipopolysaccharide (LPS). On the other hand, LPS induces PAI-1 secretion. Activation of individual cells by LPS is facilitated by CD14. The single nucleotide polymorphisms -675 4G/5G in SERPINE1 and C-159T in CD14 are major determinants of PAI-1 and CD14 expression, respectively. Objective: To evaluate the frequency of the -675 4G/5G SERPINE1 and C-159T CD14 polymorphisms in house dust mite (HDM) allergic asthma patients. Methods: The polymorphisms were evaluated in unrelated inhabitants of northeastern Poland, including 372 HDM-allergic asthmatic patients and 160 healthy nonatopic control subjects using polymerase chain reaction. Results: Both the C allele of CD14 and the 4G allele of SERPINE1 were more frequently encountered in HDM-allergic asthmatic patients than in healthy control individuals. When the 5G/5G-TT/CT genotype was considered as a nonrisk genotype, all other genotypes were associated with asthma. The odds ratios ranged from 3.96 (95% confidence interval, 1.56-10.1) for the 5G/5G-CC genotype to 10.7 (95% confidence interval, 5.1-24.9) for the 4G/4G-CC genotype. Bronchial reactivity to histamine and total serum immunoglobulin (Ig) E levels were predominantly associated with the 4G/5G SERPINE1 variants, while bronchial reactivity to Dermatophagoides pteronyssinus and serum concentrations of specific IgE against D pteronyssinus were predominantly associated with the C/T CD14 variants. Patients with 4G/4G-CC genotype had the lowest forced expiratory volume in 1 second and the highest bronchial reactivity. Conclusion: The SERPINE1 and CD14 polymorphisms studied here are associated with different aspects of bronchial reactivity and IgE response. Our results indicate that PAI-1 and CD14 may interact to affect susceptibility to allergic asthma.
| Original language | English |
|---|---|
| Pages (from-to) | 284-292 |
| Number of pages | 9 |
| Journal | Journal of investigational allergology & clinical immunology : official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología |
| Volume | 18 |
| Issue number | 4 |
| Publication status | Published - 2008 |
Keywords
- Asthma
- Genetics
- Innate immunity
- Plasminogen activator inhibitor
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology