Analysis of -675 4 g/5 G 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% 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.


CONCLUSIONS
The SERPINE1 and CD14 polymorphisms studied here are associated with different aspects of bronchial reactivity and IgE response. Our results indicate that PAl-1 and CD14 may interact to affect susceptibility to allergic asthma.
Kowal
K
K
Department of Allergology and Internal Medicine, Medical University of Bialystok, Poland. kowalkmd@amb.edu.pl
Bodzenta-Lukaszyk
A
A
Pampuch
A
A
Szmitkowski
M
M
Zukowski
S
S
Donati
M Benedetta
MB
Iacoviello
L
L
D000328:Adult; D000483:Alleles; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood*; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000276:immunology; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011044:Poland; D020641:Polymorphism, Single Nucleotide
D039741:Antigens, Dermatophagoides; D018950:Lipopolysaccharide Receptors; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D007073:Immunoglobulin E