Abstract
Oxidative stress is thought to be involved in the pathogenesis of asthma. Glutathione S-transferase (GST) enzymes play an important role in the antioxidant defence mechanism and therefore may influence asthma risk. Polymorphism of GSTT1 and GSTM1 genes has been associated with asthma in children and adults, but results are inconsistent across studies. The aim of the present study was to examine the association of GSTT1 and GSTM1 gene genotypes and the risk of asthma among 44 stable asthmatic children in comparison to 30 healthy control subjects. Genotyping was performed using the multiplex PCR technique. GSTT1 null genotype was significantly associated with an increased risk of asthma by more than 9-fold. GSTM1 polymorphism did not appear to play a major role in the development of bronchial asthma in children. Neither was associated with patients’ phenotype.
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References
Avon Longitudinal Study of Parents and Children (ALSPAC) (2004) A resource for genetic epidemiology. Eur J Endocrinol 151:U125–U129
Babusikova E, Jesenak M, Kirshnerova R et al (2009) Association of oxidative stress and GSTT1 gene with childhood bronchial asthma. J Physiol Pharmacol 5:27–30
Bajpai P, Tripatai AK, Agrawal D (2007) Increased frequencies of glutathione-S-transferase (GSTT1–GSTM1) null genotypes in Indian patients with chronic myeloid leukaemia. Leuk Res 31:1359–1363
Brasch-Andersen C, Christiansen L, Tan Q (2004) Possible gene dosage effect of glutathione-S-transferases on atopic asthma: using real-time PCR for quantification of GSTM1 and GSTT1 gene copy numbers. Hum Mutat 24:208–214
Carroll WD, Lenney W, Jones PW et al (2005) Effects of glutathione S-transferase M1, T1 and P1 on lung function in asthmatic families. Clin Exp Allergy 35(9):1155–1161
Cook DG, Strachan DP (1999) Health effects of passive smoking-10: Summary of effects of parental smoking on the respiratory health of children and implications for research. Thorax 54:357–366
Cotton SC, Sharp L, Little J, Brockton N (2000) Glutathione S-transferase polymorphisms and colorectal cancer: a HuGE review. Am J Epidemiol 151(1):7–32
Ercan H, Birben E, Dizdar EA et al (2006) Oxidative stress and genetic and epidemiologic determinants of oxidant injury in childhood asthma. J Allergy Clin Immun 118:1097–1104
Gilliland FD, Li YF, Dubeau L et al (2002) Effects of glutathione S-transferase M1, maternal smoking during pregnancy, and environmental tobacco smoke on asthma and wheezing in children. Am J Respir Crit Care Med 166:457–63
Global Initiative for Asthma (GINA) (2008) Global strategy for asthma management and prevention. Available at: www.ginasthma.org
Hanene C, Jihene L, Jamel A, Kamel H, Agnès H (2007) Association of GST genes polymorphisms with asthma in Tunisian children. Mediators Inflamm 2007:19564
Hayes JD, Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30(6):445–600
Hayes JD, Strange RC (1995) Potential contribution of the glutathione S-transferase supergene family to resistance to oxidative stress. Free Radic Res Commun 22:193–207
Hole DJ, Watt GC, Davey-Smith G (1996) Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study. BMJ 313:711–715
Holla LI, Stejskalova A, Vasku A (2006) Polymorphisms of the GSTM1 and GSTT1 genes in patients with allergic diseases in the Czech population. Allergy 61(2):265–267
Islam T, Berthane K, McConnell R et al (2009) Glutathione S-transferase (GST) P1, GSTM1, exercise, ozone and asthma incidence in school children. Thorax 64:197–202
Ivaschenko T, Sideleva O, Baranov V (2001) Glutathione-S-transferase μ and theta gene polymorphisms as new risk factors of atopic bronchial asthma. J Mol Med 80:39–43
Kabesch M, Hoefer C, Carr D et al (2004) Glutathione S-transferase deficiency and passive smoking increase childhood asthma. Thorax 59:569–573
Kamada F, Mashimo Y, Inoue H et al (2007) The GSTP1 gene is a susceptibility gene for childhood asthma and the GSTM1 gene is a modifier of the GSTP1 Gene. Int Arch Allergy Immunol 144:275–286
Lee YL, Lin YC, Lee YC, Wang JY, Hsiue TR, Guo YL (2004) Glutathione S-transferase P1 gene polymorphism and air pollution as interactive risk factors for childhood asthma. Clin Exp Allergy 34(11):1707–1713
Maddox L, Schwartz DA (2002) The pathophisiology of asthma. Annu Rev Med 53:477–498
McLellan RA, Oscarson M, Alexandrie AK et al (1997) Characterization of a human glutathione S-transferase mu cluster containing a duplicated GSTM1 gene that causes ultra-rapid enzyme activity. Mol Pharmacol 52:958–65
Ober C, Tsalenko A, Parry R, Cox NJ (2000) A second-generation genome wide screen for asthma-susceptibility alleles in a founder population. Am J Hum Genet 67(5):1154–1162
Palmer CN, Doney AS, Lee SP et al (2006) Glutathione S-transferase M1 and P1 genotype, passive smoking, and peak expiratory flow in asthma. Pediatrics 118:710–716
Rogers AJ, Brash Anderson C, Ionita-Laza I et al (2009) The interaction of glutathione S-transferase M1-null variants with tobacco smoke exposure and the development of childhood asthma. Clin Exp Allergy 39:172–179
Sandford AJ, Chan HW, Wong GWK (2004) Candidate genetic polymorphisms for asthma in Chinese schoolchildren from Hong Kong. Int J Tuberculosis Lung Dis 8:519–527
Sengler C, Lau U, Nickel R (2002) Interactions between genes and environmental factors in asthma and atopy: new developments. Respir Res 3:7–22
Sprenger R, Schlagenhaufer R, Kerb R et al (2000) Characterization of the glutathione S-transferase GSTT1 deletion: discrimination of all genotypes by polymerase chain reaction indicates a trimodular genotype–phenotype correlation. Pharmacogenetics 10:557–565
Strange RC, Jones PW, Fryer AA (2000) Glutathione S-transferase: genetics and role in toxicology. Toxicol Lett 112–113:357–363
Tamer L, Çalikoğlu M, Ates NA et al (2004) Glutathione-S-transferase gene polymorphisms (GSTT1, GSTM1, GSTP1) as increased risk factors for asthma. Respirology 9:493–498
von Mutius E (2009) Gene–environment interactions in asthma. J Allergy Clin Immunol 123:3–11
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Abd El-Aal, A.A., El-Nashar, M.M. & El-Sissy, A.H. Glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) genes polymorphism and risk of bronchial asthma in children. Comp Clin Pathol 21, 1197–1201 (2012). https://doi.org/10.1007/s00580-011-1262-z
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DOI: https://doi.org/10.1007/s00580-011-1262-z