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Impact of glutathione-S-transferase gene polymorphisms on enzyme activity, lung function and bronchial asthma susceptibility in Egyptian children
Authors:Karam Rehab A  Pasha Heba F  El-Shal Amal S  Rahman Hadeel M A  Gad Doaa M
Affiliation:Medical Biochemistry Department, Zagazig University, Zagazig, Egypt.
Abstract:

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.
Keywords:GST, glutathione-S-transferase   ROS, reactive oxygen species   PCR, polymerase chain reaction   PCR-RFLP, PCR-restriction fragment length polymorphism   FEV1, Forced expiratory volume in 1 s   FVC, forced vital capacity   CDNB, 1-chloro-2,4-dinitrobenzene
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