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

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 % confi dence interval, 1.56-10.1) for the 5G/5G-CC genotype to 10.7 (95% confi dence 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-C