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Original Article
 

Analysis of -675 4G/5G SERPINE1 and C-159T CD14 Polymorphisms in House Dust Mite-Allergic Asthma Patients
 

K Kowal,1 A Bodzenta-Lukaszyk,1 A Pampuch,1,2 M Szmitkowski,3 S Zukowski,1 M Benedetta Donati,2 L Iacoviello2

1 Department of Allergology and Internal Medicine, Medical University of Bialystok, Poland
2 Laboratory of Genetic and Environmental Epidemiology, Research Laboratories, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
3 Department of Biochemical Diagnostics, Medical University of Bialystok, Poland

J Investig Allergol Clin Immunol 2008; Vol. 18(4): 284-292
 

 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 specifi c 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.

Key words: Asthma. Genetics. Innate immunity. Plasminogen activator inhibitor.