Impact of glutathione-S-transferase gene polymorphisms on enzyme activity, lung function and bronchial asthma susceptibility in Egyptian children.
BACKGROUND
Asthma is a complex multifactorial disease with an obvious genetic predisposition. Polymorphisms of the glutathione-S-transferase (GST) genes are known risk factors for some environmentally-related diseases. The aim of the present study was to investigate the role of polymorphisms in the GSTT1, GSTM1 and GSTP1 genes and asthma susceptibility in Egyptian children, and to analyze their effect on GST activity and lung function.


METHODS
GSTT1 and GSTM1 gene polymorphism was genotyped using the multiplex polymerase chain reaction (PCR) and GSTP1 ILe105Val polymorphism was determined using PCR-restriction fragment length polymorphism (PCR-RFLP) in 168 healthy and 126 asthmatic children (82 atopic and 44 nonatopic). Also GST enzyme activity and lung function were evaluated.


RESULTS
Asthmatic children had a significant higher prevalence of the GSTM1 null (P=0.003) and significant lower prevalence of GSTP1 Val/Val genotypes (P=0.02) than control group. Lung function was significantly decreased in GSTM1 null genotype and GSTP1 Ile/Ile genotype. GSTP1 Val/Val genotypes and GSTM1 null genotype had a significant decrease in plasma GST activity.


CONCLUSIONS
GST genes polymorphisms may play an important role in pathogenesis and susceptibility to asthma in children.
Medical Biochemistry Department, Zagazig University, Zagazig, Egypt.
Rehab A
RA
Karam
Heba F
HF
Pasha
Amal S
AS
El-Shal
Hadeel M A
HM
Rahman
Doaa M
DM
Gad
D001249:Asthma / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D004534:Egypt; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000502:physiology* / Q000503:physiopathology; D008297:Male; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012143:Respiratory Physiological Phenomena / Q000235:genetics; D012307:Risk Factors
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human