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Genetic polymorphisms in the cytochromes P-450 (1A1, 2E1), microsomal epoxide hydrolase and glutathione S-transferase M1, T1, and P1 genes, and their relationship with chronic bronchitis and relapsing pneumonia in children

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Abstract

The purpose of this study was to investigate the possible roles of the genes functioning in xenobiotic metabolism and antioxidant pathways in the development of severe chronic lung disease in children. Polymorphisms in the genes encoding CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, and GSTP1 were investigated in cases of Tatar children with chronic bronchitis (n=129) and relapsing pneumonia (n=50) and in cases of ethnically matched healthy individuals (n=227) living in the city of Ufa, the Republic of Bashkortostan (South Ural region of Russia), by polymerase chain reaction–restriction fragment length polymorphism (PCR-RLFP) method. The frequency of the *2C allele of the CYP1A1 gene was significantly higher in patients than in the healthy control group (χ2=15.02, P=0.0007, Pcor=0.0021). This allele was associated with a higher risk of chronic bronchitis in children (OR 4.14, 95% CI 1.83–9.53; Pcor=0.0024). Similar results were obtained in cases of patients with relapsing pneumonia (OR 3.86, 95% CI 1.34–10.95; Pcor=0.027 for the *2C allele of the CYP1A1 gene). The frequency of the *5B allele of the CYP2E1 gene was higher in the relapsing pneumonia patients (7.0 vs 1.98% in the control group; χ2=5.68, P=0.018, Pcor=0.054; OR 3.72, 95% CI 1.21–11.24). The increase in the GSTT1 gene deletion was significant only in cases of chronic bronchitis (39.53 compared to 21.15% in the control group; χ2=12.96, P=0.001, Pcor=0.003; OR 2.44, 95% CI 1.48–4.04). Our results show that the presence of the GSTM1 gene deletion is unfavorable for the development of chronic lung disease in females (χ2=9.57; P=0.0029, Pcor=0.0116) and was associated with increased risk (OR 2.44, 95% CI 1.36–4.38). The distribution of EPHX1 and GSTP1 gene genotypes was similar in the control and patient groups. Our findings indicate that the polymorphisms of the CYP1A1, CYP2E1, and GSTT1 genes probably play a substantial part in susceptibility to severe airway and lung injury in cases of children with chronic bronchitis and relapsing pneumonia.

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Abbreviations

CYP1A1:

cytochrome P-4501A1

CYP2E1:

cytochrome P-4502E1

GSTM1:

Glutathione S-transferase

GSTT1:

Glutathione S-transferase T1

GSTP1:

Glutathione S-transferase

EPHX1:

Microsomal epoxide hydrolase

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Acknowledgements

This work was supported by the Russian Foundation for Basic Research (grant 04-04-48318a), the Russian Scientific Foundation for Humanities (04-06-00016a) and the Russian Federation President Program (grant Mκ-2755.2004). We would like to express our gratitude to the families of patients who participated in this study.

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Authors and Affiliations

  1. Institute of Biochemistry and Genetics, Ufa Scientific Center, Pr. Oktyabrya, 69, Ufa, 450054, Russia

    G. F. Korytina, D. G. Yanbaeva & T. V. Victorova

  2. Department of Pediatrics, Bashkortostan State Medical University, Lenina st., 3, Ufa, 450000, Russia

    L. I. Babenkova & E. I. Etkina

  3. Department of Biology, Bashkortostan State Medical University, Lenina st., 3, Ufa, 450000, Russia

    T. V. Victorova

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  1. G. F. Korytina
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  2. D. G. Yanbaeva
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  3. L. I. Babenkova
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  4. E. I. Etkina
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  5. T. V. Victorova
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Correspondence to G. F. Korytina.

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Korytina, G.F., Yanbaeva, D.G., Babenkova, L.I. et al. Genetic polymorphisms in the cytochromes P-450 (1A1, 2E1), microsomal epoxide hydrolase and glutathione S-transferase M1, T1, and P1 genes, and their relationship with chronic bronchitis and relapsing pneumonia in children. J Mol Med 83, 700–710 (2005). https://doi.org/10.1007/s00109-005-0660-6

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  • DOI: https://doi.org/10.1007/s00109-005-0660-6

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