Abstract
OBJECTIVE: Reactive oxygen species (ROS) contribute to oxidative lung injury. The glutathione-S-transferases (GST) family and microsomal epoxide hydrolase (mEPHx) enzymes detoxify ROS, and genetic polymorphisms alter this detoxification. We hypothesized that polymorphisms encoding for less efficient enzymes were associated with bronchopulmonary dysphasia (BPD).
STUDY DESIGN: We determined allelic distribution of these polymorphisms in a pilot study of 35 BPD cases and 98 controls. Ļ2 and regression analysis were performed.
RESULTS: GST P1 val105ile distribution differed between the groups, with the more efficient val/val allele predominately in controls (pā¤0.05). When controlling for race and sex, BPD cases were less likely to be homozygotes for the val/val isoform (OR 0.21, CI: 0.045ā0.95, p=0.04) and more likely to possess the less efficient ile isoform (OR 4.5, CI: 1.0ā20.7, p=0.05).
CONCLUSIONS: This pilot study suggests that BPD is associated with the presence of the GST-P1 105ile allele. Future prospective studies are warranted.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Jobe AH, Bancalari E . Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723ā1729.
Lemons JA, Bauer CR, Oh W et al. Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996. NICHD Neonatal Research Network. Pediatrics 2001;107:E1.
Hallman M, Haataja, R . Genetic influences and neonatal lung disease. Semin Neonatol 2003;8:19ā27.
Parker RA, Lindstrom DP, Cotton RB . Evidence from twin study implies possible genetic susceptibility to bronchopulmonary dysplasia. Semin Perinatol 1996;20:206ā209.
Strange RC, Spiteri MA, Ramachandran S, Fryer AA . Glutathione-S-transferase family of enzymes. Mutat Res 2001;482:21ā26.
Salinas AE, Wong MG . Glutathione S-transferases ā a review. Curr Med Chem 1999;6:279ā309.
Rushmore TH, Pickett CB . Glutathione S-transferases, structure, regulation, and therapeutic implications. J Biol Chem 1993;268:11475ā11478.
Rahman Q, Abidi P, Afaq F et al. Glutathione redox system in oxidative lung injury. Crit Rev Toxicol 1999;29:543ā568.
Fryer AA, Bianco A, Hepple M et al. Polymorphism at the glutathione S-transferase GSTP1 locus. A new marker for bronchial hyperresponsiveness and asthma. Am J Respir Crit Care Med 2000;161:1437ā1442.
Smith CA, Harrison DJ . Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema. Lancet 1997;350:630ā633.
Zhou W, Thurston SW, Liu G et al. The interaction between microsomal epoxide hydrolase polymorphisms and cumulative cigarette smoking in different histological subtypes of lung cancer. Cancer Epidemiol Biomarkers Prev 2001;10:461ā466.
Yim JJ, Park GY, Lee CT et al. Genetic susceptibility to chronic obstructive pulmonary disease in Koreans: combined analysis of polymorphic genotypes for microsomal epoxide hydrolase and glutathione S-transferase M1 and T1. Thorax 2000;55:121ā125.
Spiteri MA, Bianco A, Strange RC, Fryer AA . Polymorphisms at the glutathione S-transferase, GSTP1 locus: a novel mechanism for susceptibility and development of atopic airway inflammation. Allergy 2000;55:15ā20.
Sandford AJ, Weir TD, Pare PD . Genetic risk factors for chronic obstructive pulmonary disease. Eur Respir J 1997;10:1380ā1391.
Hayes JD, Strange RC . Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 2000;64:154ā166.
Hayes JD, McLellan LI . Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defense against oxidative stress. Free Radic Res 1999;31:273ā300.
Gilliland FD, Gauderman WJ, Vora H, Rappaport E, Dubeau L . Effects of glutathione S-transferase M1, T1, and P1 on childhood lung function growth. Am J Respir Crit Care Med 2002;166:710ā716.
Gilliland FD, Rappaport EB, Berthane K et al. Effects of glutathione S-transferase P1, M1 and T1 on acute respiratory illness in school children. Am J Respir Crit Care Med 2002;166:346ā351.
Chen CL, Liu Q, Relling MV . Simultaneous characterization of glutathione S-transferase M1 and T1 polymorphisms by polymerase chain reaction in American whites and blacks. Pharmcogenetics 1996;6:187ā191.
Vavilin VA, Chasovnikova OB, Liakhovich VV, Gavalov SM, Riabova OA . [Genetic polymorphism in glutathione S-transferase M1 and T1 in children with bronchial asthma]. Vopr Med Khim 2000;46:388ā397.
Nelson HH, Wiencke JK, Christiani DC et al. Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase. Carcinogenesis 1995;16:1243ā1245.
Harries JW, Stubbins MJ, Forman D, Howard GC, Wolf CR . Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 1997;18: 641ā644.
Nickerson BG, Taussig LM . Family history of asthma in infants with bronchopulmonary dysplasia. Pediatrics 1980;65:1140ā1144.
Nickerson B . Bronchopulmonary dysplasia and family history of asthma. Pediatr Pulmonol 1995;20:276ā279.
Evans M, Palta M, Sadek M, Weinstein MR, Peters ME . Associations between family history of asthma, bronchopulmonary dysplasia and childhood asthma in very low birth weight children. Am J Epidemiol 1998;148:460ā466.
Uchida K . Induction of glutathione S-transferase by prostaglandins. Mech Ageing Dev. 2000;116:135ā140.
Jain A, Mehta T, Auld PA et al. Glutathione metabolism in newborns: evidence for glutathione deficiency in plasma, bronchoalveolar lavage fluid and lymphocytes in prematures. Pediatr Pulmonol. 1995;20:160ā166.
Frank L, Sosenko, IR . Failure of premature rabbits to increase antioxidant enzymes during hyperoxic exposure: increased susceptibility to pulmonary oxygen toxicity compared with term rabbits. Pediatr Res 1991;29:292ā296.
Varga SJ, Matkovics B, Pataki L, Molnar A, Novak Z . Comparison of antioxidant red blood cell enzymes in premature and full-term neonates. Clin Chim Acta 1985;147:191ā195.
Karmazsin L, Olah VA, Balla G, Makay A . Serum antioxidant activity in premature babies. Acta Paediatr Hung 1991;30:217ā224.
Welty SE, Smith CV . Rationale for antioxidant therapy in premature infants to prevent bronchopulmonary dysplasia. Nutr Rev 2001;59:10ā17.
Brown LAS, Perez JA, Harris FL, Clark RH . Glutathione supplements protect preterm rabbits from oxidative lung injury. Am J Physiol 1996;270:L446āL451.
Frank L, Bucher JR, Roberts RJ . Oxygen toxicity in neonatal and adult animals of various species. J Appl Physiol 1978;45:699ā704.
Van Lieshout EM, Knapen MF, Lange WP, Steegers EA, Peters WH . Localization of glutathione S-transferase alpha and pi in human embryonic tissues at 8 weeks gestational age. Hum Reprod 1998;13:1380ā1386.
Acknowledgements
We thank Dr. Neal Simon, Juanita Davis, and Lynne Wineski, as well as Dr. Burt Lesnick, Charmaine Coulen, and Mary LeBlanc, of Georgia Pediatric Pulmonology Associates for sample collection. We also thank Dr. Kevin Sullivan for statistical direction and Frank Harris in the Emory University Neonatology Laboratory for his technical assistance.
Author information
Authors and Affiliations
Additional information
This study was supported by Emory/Egleston Children's Research, NIH R03 HD37674.
Rights and permissions
About this article
Cite this article
Manar, M., Brown, M., Gauthier, T. et al. Association of Glutathione-S-Transferase-P1 (GST-P1) Polymorphisms with Bronchopulmonary Dysplasia. J Perinatol 24, 30ā35 (2004). https://doi.org/10.1038/sj.jp.7211020
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.jp.7211020
This article is cited by
-
Verification of immunology-related genetic associations in BPD supports ABCA3 and five other genes
Pediatric Research (2022)
-
Recurrent copy number variants associated with bronchopulmonary dysplasia
Pediatric Research (2016)
-
Zingerone protects against cisplatin-induced oxidative damage in the jejunum of Wistar rats
Oriental Pharmacy and Experimental Medicine (2015)
-
Association of Nrf2 with airway pathogenesis: lessons learned from genetic mouse models
Archives of Toxicology (2015)
-
Glutathione-S-transferase-P1 I105V polymorphism and response to antenatal betamethasone in the prevention of respiratory distress syndrome
European Journal of Clinical Pharmacology (2009)