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.
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 (chi2=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; chi2=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; chi2=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 (chi2=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.
Korytina
G F
GF
Institute of Biochemistry and Genetics, Ufa Scientific Center, Pr. Oktyabrya, 69, Ufa, 450054, Russia. Guly_Kory@mail.ru
Yanbaeva
D G
DG
Babenkova
L I
LI
Etkina
E I
EI
Victorova
T V
TV
D000293:Adolescent; D000975:Antioxidants / Q000378:metabolism; D001991:Bronchitis / Q000235:genetics* / Q000378:metabolism; D002648:Child; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D011014:Pneumonia / Q000235:genetics* / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length; D012008:Recurrence; D015262:Xenobiotics / Q000378:metabolism
D000975:Antioxidants; D015262:Xenobiotics; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases