Skip to main content

Advertisement

SpringerLink
Log in

Glutathione-S-transferase-P1 I105V polymorphism and response to antenatal betamethasone in the prevention of respiratory distress syndrome

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The aim of this pilot study was to assess the association between polymorphisms in genes that encode for proteins involved in the pharmacokinetics/pharmacodynamics of glucocorticoids and the occurrence of respiratory distress syndrome (RDS) in preterm infants born to mothers treated with a complete course of betamethasone.

Methods

Sixty-two preterm infants were enrolled. The C1236T, G2677T, and C3435T polymorphisms in the ABCB1 gene, BclI, N363S and ER22/23EK in the NR3C1 gene, I105V in the GST-P1 gene and GST-M1 and GST-T1 deletions were analyzed, and their association with the occurrence of RDS was assessed.

Results

In univariate analysis, the heterozygous and homozygous presence of the I105V variant in the GST-P1 gene seemed to confer protection against the occurrence of RDS (P = 0.032), while no association for all other polymorphisms was observed. In multivariate analysis, selection from the reference model of independent variables based on AIC (Akaike information criteria) maintained three variables in the model: gestation, C3435T, and GST-P1 genotype.

Conclusions

Polymorphisms of the GST-P1 gene may influence the effect of antenatal steroids on the newborn lung.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Slattery MM, Morrison JJ (2002) Preterm delivery. Lancet 360:1489–1497

    Article  PubMed  Google Scholar 

  2. Roberts D, Dalziel S (2006) Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 3:CD004454

    PubMed  CAS  Google Scholar 

  3. Lemons JA, Bauer CR, Oh W et al (2001) 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 107:E1

    Article  PubMed  CAS  Google Scholar 

  4. Avery ME, Mead J (1959) Surface properties in relation to atelectasis and hyaline membrane disease. AMA J Dis Child 97:517–523

    PubMed  CAS  Google Scholar 

  5. Vyas J, Kotecha S (1997) Effects of antenatal and postnatal corticosteroids on the preterm lung. Arch Dis Child Fetal Neonatal Ed 77:F147–150

    Article  PubMed  CAS  Google Scholar 

  6. Seckl JR (2001) Glucocorticoid programming of the fetus; adult phenotypes and molecular mechanisms. Mol Cell Endocrinol 185:61–71

    Article  PubMed  CAS  Google Scholar 

  7. Mark PJ, Waddell BJ (2006) P-glycoprotein restricts access of cortisol and dexamethasone to the glucocorticoid receptor in placental BeWo cells. Endocrinology 147:5147–5152

    Article  PubMed  CAS  Google Scholar 

  8. Pacifici GM, Nottoli R (1995) Placental transfer of drugs administered to the mother. Clin Pharmacokinet 28:235–269

    Article  PubMed  CAS  Google Scholar 

  9. Collier AC, Tingle MD, Paxton JW et al (2002) Metabolizing enzyme localization and activities in the first trimester human placenta: the effect of maternal and gestational age, smoking and alcohol consumption. Hum Reprod 17:2564–2572

    Article  PubMed  CAS  Google Scholar 

  10. Molsa M, Heikkinen T, Hakkola J et al (2005) Functional role of P-glycoprotein in the human blood-placental barrier. Clin Pharmacol Ther 78:123–131

    Article  PubMed  CAS  Google Scholar 

  11. Ceckova-Novotna M, Pavek P, Staud F (2006) P-glycoprotein in the placenta: expression, localization, regulation and function. Reprod Toxicol 22:400–410

    Article  PubMed  CAS  Google Scholar 

  12. Leslie EM, Deeley RG, Cole SP (2005) Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 204:216–237

    Article  PubMed  CAS  Google Scholar 

  13. Ueda K, Okamura N, Hirai M et al (1992) Human P-glycoprotein transports cortisol, aldosterone and dexamethasone, but not progesterone. J Biol Chem 267:24248–24252

    PubMed  CAS  Google Scholar 

  14. Marzolini C, Paus E, Buclin T et al (2004) Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther 75:13–33

    Article  PubMed  CAS  Google Scholar 

  15. Hoffmeyer S, Burk O, vonRichter O et al (2000) Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 97:3473–3478

    Article  PubMed  CAS  Google Scholar 

  16. van Rossum EF, Binder EB, Majer M et al (2006) Polymorphisms of the glucocorticoid receptor gene and major depression. Biol Psychiatry 59:681–688

    Article  PubMed  CAS  Google Scholar 

  17. van Rossum EF, Koper JW, van den Beld AW et al (2003) Identification of the bclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index. Clin Endocrinol 59:585–592

    Article  Google Scholar 

  18. van Rossum EF, Voorhoeve PG, te Velde SJ et al (2004) The ER22/23EK polymorphism in the glucocorticoid receptor gene is associated with a beneficial body composition and muscle strength in young adults. J Clin Endocrinol Metab 89:4004–4009

    Article  PubMed  CAS  Google Scholar 

  19. Daly AK (2003) Pharmacogenetics of the major polymorphic metabolizing enzymes. Fundam Clin Pharmacol 17:27–41

    Article  PubMed  CAS  Google Scholar 

  20. Maruyama H, Listowsky I (1984) Preferential binding of steroids by anionic forms of rat glutathione S-transferase. J Biol Chem 259:12449–12455

    PubMed  CAS  Google Scholar 

  21. Homma H, Listowsky I (1985) Identification of yb-glutathione-S-transferase as a major rat liver protein labeled with dexamethasone 21-methanesulfonate. Proc Natl Acad Sci USA 82:7165–7169

    Article  PubMed  CAS  Google Scholar 

  22. Homma H, Maruyama H, Niitsu Y et al (1986) A subclass of glutathione S-transferases as intracellular high-capacity and high-affinity steroid-binding proteins. Biochem J 235:763–768

    PubMed  CAS  Google Scholar 

  23. Listowsky I (1993) High capacity binding by glutathione S-transferases and glucocorticoid resistance. In: Tew KD, Pickett CB, Mantle TJ, Mannervik B, Hayes JD (eds) Structure and function of glutathione transferases. CRC Press, Boca Raton, pp 199–205

    Google Scholar 

  24. Strange RC, Spiteri MA, Ramachandran S et al (2001) Glutathione-S-transferase family of enzymes. Mutat Res 482:21–26

    PubMed  CAS  Google Scholar 

  25. Anderer G, Schrappe M, Brechlin AM et al (2000) Polymorphisms within glutathione S-transferase genes and initial response to glucocorticoids in childhood acute lymphoblastic leukaemia. Pharmacogenetics 10:715–726

    Article  PubMed  CAS  Google Scholar 

  26. Manar MH, Brown MR, Gauthier TW et al (2004) Association of glutathione-S-transferase-P1 (GST-P1) polymorphisms with bronchopulmonary dysplasia. J Perinatol 24:30–35

    Article  PubMed  CAS  Google Scholar 

  27. Anonymous (1995) Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH consensus development panel on the effect of corticosteroids for fetal maturation on perinatal outcomes. JAMA 273:413–418

  28. Cascorbi I, Gerloff T, Johne A et al (2001) Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther 69:169–174

    Article  PubMed  CAS  Google Scholar 

  29. Wasilewska A, Zalewski G, Chyczewski L et al (2007) MDR-1 gene polymorphisms and clinical course of steroid-responsive nephrotic syndrome in children. Pediatric Nephrol 22:44–51

    Article  Google Scholar 

  30. Bachmann AW, Sedgley TL, Jackson RV et al (2005) Glucocorticoid receptor polymorphisms and post-traumatic stress disorder. Psychoneuroendocrinology 30:297–306

    Article  PubMed  CAS  Google Scholar 

  31. Koper JW, Stolk RP, de Lange P et al (1997) Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance. Hum Genet 99:663–668

    Article  PubMed  CAS  Google Scholar 

  32. Harries LW, Stubbins MJ, Forman D et al (1997) Identification of genetic polymorphisms at the glutathione S-transferase pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 18:641–644

    Article  PubMed  CAS  Google Scholar 

  33. Chen CL, Liu Q, Pui CH et al (1997) Higher frequency of glutathione S-transferase deletions in black children with acute lymphoblastic leukemia. Blood 89:1701–1707

    PubMed  CAS  Google Scholar 

  34. Crowley PA (1995) Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol 173:322–335

    Article  PubMed  CAS  Google Scholar 

  35. Baud O, Foix-L’Helias L, Kaminski M et al (1999) Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants. N Engl J Med 341:1190–1196

    Article  PubMed  CAS  Google Scholar 

  36. Elimian A, Garry D, Figueroa R et al (2007) Antenatal betamethasone compared with dexamethasone (betacode trial): a randomized controlled trial. Obstet Gynecol 110:26–30

    PubMed  CAS  Google Scholar 

  37. Wen SW, Smith G, Yang Q et al (2004) Epidemiology of preterm birth and neonatal outcome. Semin Fetal Neonatal Med 9:429–435

    Article  PubMed  Google Scholar 

  38. Anyaegbunam WI, Adetona AB (1997) Use of antenatal corticosteroids for fetal maturation in preterm infants. Am Fam Physician 56:1093–1096

    PubMed  CAS  Google Scholar 

  39. Di Blasio AM, van Rossum EF, Maestrini S et al (2003) The relation between two polymorphisms in the glucocorticoid receptor gene and body mass index, blood pressure and cholesterol in obese patients. Clin Endocrinol 59:68–74

    Article  Google Scholar 

  40. Huizenga NA, Koper JW, De Lange P et al (1998) A polymorphism in the glucocorticoid receptor gene may be associated with an increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab 83:144–151

    Article  PubMed  CAS  Google Scholar 

  41. Gruol DJ, Bourgeois S (1997) Chemosensitizing steroids: glucocorticoid receptor agonists capable of inhibiting P-glycoprotein function. Cancer Res 57:720–727

    PubMed  CAS  Google Scholar 

  42. Yates CR, Chang C, Kearbey JD et al (2003) Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res 20:1794–1803

    Article  PubMed  CAS  Google Scholar 

  43. Sugawara I, Kataoka I, Morishita T et al (1988) Tissue distribution of P-glycoprotein encoded by a multidrug-resistant gene as revealed by a monoclonal antibody, MRK 16. Cancer Res 48:1926–1929

    PubMed  CAS  Google Scholar 

  44. Cordon-Cardo C, O’Brien JP, Casals D et al (1989) Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci USA 86:695–698

    Article  PubMed  CAS  Google Scholar 

  45. Nakamura Y, Ikeda S, Furukawa T et al (1997) Function of P-glycoprotein expressed in placenta and mole. Biochem Biophys Res Commun 235:849–853

    Article  PubMed  CAS  Google Scholar 

  46. Sugawara I, Akiyama S, Scheper RJ et al (1997) Lung resistance protein (LRP) expression in human normal tissues in comparison with that of MDR1 and MRP. Cancer Lett 112:23–31

    Article  PubMed  CAS  Google Scholar 

  47. Farrell RJ, Murphy A, Long A et al (2000) High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy. Gastroenterology 118:279–288

    Article  PubMed  CAS  Google Scholar 

  48. Wasilewska AM, Zoch-Zwierz WM, Pietruczuk M (2006) Expression of P-glycoprotein in lymphocytes of children with nephrotic syndrome treated with glucocorticoids. Eur J Pediatr 165:839–844

    Article  PubMed  CAS  Google Scholar 

  49. Kimchi-Sarfaty C, Oh JM, Kim IW et al (2007) A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science 315:525–528

    Article  PubMed  CAS  Google Scholar 

  50. Syme MR, Paxton JW, Keelan JA (2004) Drug transfer and metabolism by the human placenta. Clin Pharmacokinet 43:487–514

    Article  PubMed  CAS  Google Scholar 

  51. van Lieshout EM, Knapen MF, Lange WP et al (1998) Localization of glutathione S-transferases alpha and pi in human embryonic tissues at 8 weeks gestational age. Hum Reprod 13:1380–1386

    Article  PubMed  Google Scholar 

  52. Stanulla M, Schrappe M, Brechlin AM et al (2000) Polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study. Blood 95:1222–1228

    PubMed  CAS  Google Scholar 

  53. Cotton SC, Sharp L, Little J et al (2000) Glutathione S-transferase polymorphisms and colorectal cancer: a huge review. Am J Epidemiol 151:7–32

    PubMed  CAS  Google Scholar 

  54. Verlaan M, te Morsche RH, Roelofs HM et al (2003) Glutathione S-transferase mu null genotype affords protection against alcohol induced chronic pancreatitis. Am J Med Genet A 120A:34–39

    Article  PubMed  Google Scholar 

  55. Steisslinger HW, Pfleiderer G (1988) Acidic and basic forms of glutathione S-transferases from human placenta and comparison with human kidney glutathione S-transferase. Enzyme 40:1–6

    PubMed  CAS  Google Scholar 

  56. Watson MA, Stewart RK, Smith GB et al (1998) Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis 19:275–280

    Article  PubMed  CAS  Google Scholar 

  57. Stanulla M, Schaffeler E, Arens S et al (2005) GSTP1 and MDR1 genotypes and central nervous system relapse in childhood acute lymphoblastic leukemia. Int J Hematol 81:39–44

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Dr. Sara Marino and Dr. Sara De Iudicibus are recipients of a research fellowship from IRCCS Burlo Garofolo, Trieste. Dr. Gabriele Stocco is a recipient of a postdoctoral fellowship from the University of Trieste.

Author information

Authors and Affiliations

  1. Division of Neonatology, Burlo Garofolo Children’s Hospital, Trieste, I-34137, Italy

    Chiara Oretti & Sergio Demarini

  2. Department of Life Sciences, University of Trieste, Trieste, I-34127, Italy

    Sara Marino, Sara De Iudicibus, Ilenia Drigo, Gabriele Stocco & Giuliana Decorti

  3. Department of Reproductive and Developmental Science, Burlo Garofolo Children’s Hospital, Trieste, I-34137, Italy

    Sara Marino, Sara De Iudicibus, Ilenia Drigo & Fiora Bartoli

  4. Division of Neonatology, Clinica Mangiagalli, Milan, I-20122, Italy

    Fabio Mosca & Maria Rosa Colnaghi

Authors
  1. Chiara Oretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Marino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fabio Mosca
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Rosa Colnaghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sara De Iudicibus
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ilenia Drigo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gabriele Stocco
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fiora Bartoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Giuliana Decorti
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sergio Demarini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giuliana Decorti.

Additional information

Chiara Oretti and Sara Marino contributed equally to this manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oretti, C., Marino, S., Mosca, F. et al. Glutathione-S-transferase-P1 I105V polymorphism and response to antenatal betamethasone in the prevention of respiratory distress syndrome. Eur J Clin Pharmacol 65, 483–491 (2009). https://doi.org/10.1007/s00228-009-0617-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-009-0617-8

Keywords

Search

Navigation