Genetic variation of myeloperoxidase gene contributes to atopic asthma susceptibility: a preliminary association study in Russian population.
BACKGROUND
Recently, we have shown that both antioxidant and oxidant genes are proper candidates for asthma susceptibility genes.


OBJECTIVE
In the present study we investigated whether a common polymorphism -463G > A in the promoter of myeloperoxidase (MPO) gene, an enzyme producing hypohalogenic oxidants, is associated with the risk of bronchial asthma.


METHODS
We studied 429 unrelated Russian subjects including 215 asthmatic patients and 214 sex- and age-matched healthy controls from Central Russia. The genotyping of the polymorphism -463G > A in the MPO gene was performed by the polymerase chain reaction and the restriction fragment length polymorphism assays.


RESULTS
It was found that a carriage of a -463A allele is associated with decreased risk of asthma (OR 0.64 95%CI 0.44-0.91, p = 0.013). Furthermore, variant genotypes (-463GA + AA) of the MPO gene were associated with decreased risk of asthma (OR adjusted by age, gender, and immunoglobulin E (IgE) level was 0.63 95%CI 0.42-0.95), but at a borderline statistical significance (Bonferroni corrected p = 0.017). Further analysis revealed that both a -463A allele and the -463GA/AA genotypes are significantly associated with decreased risk of atopic asthma (p = 0.01). No association of the -463G > A polymorphism of the MPO gene with non-atopic asthma has been revealed. We also found that the allele -463A (OR = 0.47 95%CI 0.27-0.81, p = 0.01) and the -463GA + AA genotypes (OR 0.43 95%CI 0.24-0.78, p = 0.005) are significantly associated with decreased risk of late-onset atopic asthma (the disease onset after 30 years). No association of both allele and genotypes of the polymorphism -463G > A of the MPO gene with early-onset of atopic and non-atopic asthma (the disease before 30 years) was seen.


CONCLUSIONS
The results of this study provide novel insights into pathogenesis of bronchial asthma. We put forward a suggestion about a possible mechanism by which the -463G > A polymorphism of the MPO gene is involved into pathogenesis of asthma.
Polonikov
A V
AV
Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Karl Marx Street, 3, Kursk 305041, Russian Federation. polonikov@rambler.ru
Solodilova
M A
MA
Ivanov
V P
VP
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D012426:Russia; D055815:Young Adult
D009195:Peroxidase