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.

Institute of Genetics and Cytology NASB, Minsk, Belarus
Belarusian Medical Academy of Post-Graduate Education, Minsk, Belarus

The aim of the study was to investigate association of gene polymorphism of allergens metabolising enzymes glutathione-S-transferases (GST) and N-acetyltransferase-2 (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. PCR-RFLP and multiplex PCR methods were used for studying polymorphism of genes: GSTT1 (deletion), GSTM1 (deletion), GSTР1 (А313G) 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.