Effect of age and gender on susceptibility to bronchial asthma in children with different GSTM1, GSTT1 and NAT2 genotypes
Abstract
Ninety-five bronchial asthmatic children (64 boys and 31 girls aged 6-15 years) and 97 healthy children (56 boys and 41 girls aged 5-14 years) were examined. A frequencies of alleles NAT2*5, NAT2*6 of arylamine N-acetyltransferase gene (NAT2) and homozygous deletions in glutethione S-transferase p (GSTM1"-") and 0 (GSTT1"-") genes were estimated. Age and gender were shown to influence on risk of bronchial asthma occurrence associated with these genotypes. NAT2*5 allele was associated with resistance to bronchial asthma. This interrelationship was stronger in girls and weakened with maturation. NAT2*6 allele was associated with susceptibility to asthma. The value of this interrelationship was also stronger in girls and dropped with maturation. The risk significance of GSTM1"-" genotype increased with maturation and was greater in girls. The risk significance of GSTT1"-" decreased in girls and rose in boys with maturation. Interaction of these features and an impact of smoking were analysed.
About the Authors
S. I. Makarova
Институт молекулярной биологии и биофизики СО РАМН
Russian Federation
Russian Federation
V. A. Vavilin
Институт молекулярной биологии и биофизики СО РАМН
Russian Federation
Russian Federation
O. B. Chasovnikova
Институт молекулярной биологии и биофизики СО РАМН
Russian Federation
Russian Federation
S. M. Gavalov
кафедра педиатрии ФУВ Новосибирской государственной медицинской академии
Russian Federation
Russian Federation
O. A. Ryabova
кафедра педиатрии ФУВ Новосибирской государственной медицинской академии
Russian Federation
Russian Federation
V. V. Lyakhovich
Институт молекулярной биологии и биофизики СО РАМН
Russian Federation
Russian Federation
References
1. Бронхиальная астма. Глобальная стратегия. Пульмонология 1996; Прил.: 1-166.
2. Вавилин В.А., Часовникова О.В., Ляхович В.В. и др. Генетический полиморфизм глутатион S -трансферазы M l и Т1 у детей, больных бронхиальной астмой. Вопр. мед. химии 2000; 46 (4): 388-397.
3. Волков В.Т., Стрелис А.К. Бронхиальная астма. Томск; 1996.
4. Гавалов С.М., Рябова О.А., Вавилин В.А. и др. Ассоциация полиморфизма генов ферментов биотрансформации и детоксикации ксенобиотиков с особенностями бронхиальной астмы у детей. Аллергология 2000; 3: 14-21.
5. Иванова В.В., Буловская Л.Н., Железникова Г.Ф., Дробаченко О.А. Особенности иммунометаболических взаимоотношений у детей, переносящих респираторно-вирусные инфекции. Иммунология 1997; 6: 45-47.
6. Лильин Е.Т., Трубников В.И., Ванюков М.М. Введение в современную фармакогенетику. М.: Медицина; 1984.
7. Ляхович В.В., Вавилин В.А., Макарова С.И. и др. Роль ферментов биотрансформации ксенобиотиков в предрасположенности к бронхиальной астме и формировании особенностей ее клинического фенотипа. Вестн. РА М Н 2000; 12: 36-41.
8. Ляхович В.В., Вавилин В.А., Гуткина И.И. и др. Гены и ферменты системы метаболизма ксенобиотиков в онкопатологии. Вопр. мед. химии 1997; 5: 330-338.
9. Макарова С.И., Вавилин В.А., Ляхович В.В., Гавалов С.М. Аллель NAT2*5 — фактор устойчивости к заболеванию бронхиальной астмой у детей. Бюл. экспер. биол. 2000; 129 (6): 677-679.
10. Duzhak Т., Mitrofanov D., Ostashevskii V. et at. Genetic polymorphisms of CYP2D6, CYP1A1, GSTM1 and p53 genes in a unique Siberian population of tundra nentsi. Pharmacogenetics 2000; 10: 1-7.
11. Estrada-Rodgers L., Levy G.N., Weber W.W. Characterization of a hormone response element in the mouse N-acetyltransferase 2 (NAT2) promotor. Gene Expr. 1998; 7(1): 13-24.
12. Harnbali Z., Ngah W.Z., Wahid S.A., Kadir K.A. Effect of ovariectomy and sex hormone replacement on glutathione and glutathione-related enzymes in rat hepatocarcinogenesis. Pathology 1995; 27 (1): 30-35.
13. Hudson C.E., Dellaven J.E., Schulte B.A., Norris J.S. Exogenous 17beta-estradiol blocks alpha and mu but not pi class glutathione S-transferase immunoreactivity in epithelium of Syrian hamster vas deferens. J. Histochem. Cytochem. 1999; 47 (1): 91-98.
14. Infante-Rivard C., Gauthrin D., Mato J.L., Suissa S. Maternal smoking and childhood asthma. Am. J. Epidemiol. 1999; 150: 529-531.
15. Menendez-Pelaez A., Nonaka K.O., Hoffman R.A. et at. Effect of prepubertal manipulation with androgens on the development of sexual differences in the harderian giands of Syrian Hamstrs. Int. J. Dev. Biol. 1991; 35 (2): 133-138.
16. Okatani Y., Hayashi K., Watanabe K. et at. Estrogen modulates the nocturnal syntesis of melatonin in peripubertal female rats. J. Pineal Res. 1998; 24 (4): 224-229.
17. Orzechovska-Juzwenko K., Milejski P., Patkowski J. et at. Acetylator phenotype in patient with allergic diseases and its clinical significance. Intern. J. Clin. Pharmacol. Ther. Toxicol. 1990; 28 (10): 420-425.
18. Serino I., Monteleone P., d’Istria M. Effect of gonadoectomy and temperature on the N-acetyltransferase actyvity in the har derian gland of the green frog Rana esculenta. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 1995; 110 (1): 33-36.
19. Siegmung W., Hanke W., Zschiesche M. et at. N-acetylation and debrisoquine type oxidation polymorphism in Caucasians — with reference to age and sex. Intern. J. Clin. Pharmacol. Ther. Toxicol. 1990; 28 (12): 504-509.
20. Smolen T.N., Brewer J.A., Weber W.W. Testosterone modulation of N-acetylation in mouse kidney. J". Pharmacol. Exp. Ther. 1993; 264 (2): 854-858.
21. Srivastava S.K., Ни X., Xia H. et at. Metabolic fate of glutathione conjugate of benzo[a]pyrene-(7R,8S)-diol (9S,10R)-epox ide in human liver. Arch. Biochem. Biophys. 1999; 371 (2): 340-344.
22. Staffas L., Ellis E.M., Hayes J.D., Lundgren B., Depierre J.W., Mankowitz L. Growth hormone- and testosterone-dependent regulation of glutathione transferase subunit A5 in rat liver. Biochem. J. 1998; 332 (3): 763-768.
23. Van T Klooster G.A.E., Van Seeventer P.B., Kolker H.E. Highperformance liquid chromatographic method for the routine determination of sulphadimidine, its hydroxy metabolites and N4-acetylsulphadi-midine in body fluids and cell culture media. J. Chromatogr. 1991; 571 (1-2): 157-168.
24. Zielinska E., Niewiarowski W., Bodalski G. et al. Arylamine N-acetyltransferase (NAT2) gene mutations in children with allergic diseases. Clin. Pharmacol.Ther. 1997; 62 (6): 635-642.
Review
For citations:
Makarova S.I., Vavilin V.A., Chasovnikova O.B., Gavalov S.M., Ryabova O.A., Lyakhovich V.V. Effect of age and gender on susceptibility to bronchial asthma in children with different GSTM1, GSTT1 and NAT2 genotypes. PULMONOLOGIYA. 2002;(5):46-52. (In Russ.)
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