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International journal of Immunopathology, allergology, infectology.

Genetic polymorphism of allergens metabolising enzymes and predisposition to bronchial asthma in children

Chakova N.N., Krupnova E.V., Mikhalenka E.P., Chebotareva N.V., Mikulchyk N.N., Bialiayeva L.M.

The aim of the study was to investigate association of gene polymorphism of allergens metabolising enzymes glutathione Stransferases (GST) and Nacetyltransferase2 (NAT2) with predisposition to bronchial asthma (BA) in children. A total of 209 children suffering from atopic BA and 218 persons from the control group were examined. PCRRFLP and multiplex PCR methods were used for studying polymorphism of genes: GSTT1 (deletion), GSTM1 (deletion), GST1 (313G) and NAT2 (C481T, G590A).
It is revealed, that the effect of genetic polymorphism of metabolic enzymes on BA emergence depends of sex child. As for boys, the most significant gene is GSTP1, while homozygous deletion in the GSTM1 gene enhances the effect GSTP1 genotype: combination of genotypes GSTP1(AA)/ GSTM1() (OR=0,47; 2=6,02; p=0,01) has a protective effect, and the presence of genotype GSTP1(GG) (OR=4,20; p=0,005), especially GSTP1(GG)/GSTM1() genotypes combination (OR=19,88, 2=7,29, p=0,007), increases the risk of developing asthma. As for girls, the determining genetic factor is haplotype of NAT2 gene, but GSTP1 genotype modifies the risk of developing the disease: genotype NAT2(481CT) (OR=0,39; 2=7,48, p=0,006) and NAT2(CT)/GSTP1(A) genotypes combination (OR=0,34; 2=10,16; p=0,001) have protective effect, and the haplotype NAT2(CC)/NAT2(GA) (OR=3,77; 2=5,03; p=0,02) and the combination of genotypes NAT2(CC)/GSTP1(AG) (OR=3,19; 2=4,81; p=0,03) increase risk of BA emergence. Thus, it is necessary to use a different genetic testing algorithm to determine the susceptibility to asthma for boys and girls.

Keywords

Predisposition to bronchial asthma, genetic polymorphism, allergens metabolising enzymes

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Reference

Chakova N.N., Krupnova E.V., Mikhalenka E.P., Chebotareva N.V., Mikulchyk N.N., Bialiayeva L.M. Immunopathology, allergology, infectology 2013; 2:38-46