Skip to main content

Advertisement

SpringerLink
Log in

GSTT1 and GSTM1 Gene Polymorphisms as Major Risk Factors for Asthma in a North Indian Population

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Background

According to the National Family Health Survey, asthma is one of the leading diseases in India. In order to understand the complexity of asthma, the susceptibility genes need to be targeted for their association. Glutathione S-transferases play a major role in the detoxification of metabolites of oxidative stress resulting in inflammation and asthma. In the present study, the hypothesis that GSTT1 and GSTM1 gene polymorphisms are associated with asthma was examined.

Methods

This is the first study to investigate the role of GSTT1 and GSTM1 gene polymorphisms in asthma pathogenesis in a North Indian population. A total of 824 subjects were recruited, of which 410 were asthma patients, including 323 patients suffering from allergic rhinitis. The other 414 recruits were healthy controls from regions of North India. Multiplex PCR was used for genotyping the GSTT1 and GSTM1 gene polymorphisms.

Results

The GSTT1 null allele was more prevalent in asthma patients (40 %) than in the control subjects (13.3 %), which yielded a nearly fourfold risk towards asthma with odds ratio (OR) (95 % CI) = 4.35 (3.04–6.24), χ2 = 75.34, and p = 0.000. The GSTM1 polymorphism also revealed a greater prevalence of the GSTM1 null allele in asthma patients (46.6 %) than in controls (39.4 %). Statistical analysis yielded a marginal risk toward asthma with OR (95 % CI) = 1.34 (1.01–1.79), χ2 = 4.37, and p = 0.036.

Conclusions

Polymorphisms as a result of deletions in the GSTT1 and GSTM1 genes confer an increased risk towards asthma thereby suggesting the protective role of these functional genes in the development of the disease.

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

Fig. 1

Similar content being viewed by others

References

  1. Arand M, Muhlbauer R, Hengstler J et al (1996) A multiplex polymerase chain reaction protocol for the simultaneous analysis of the glutathione-S-transferase GSTM1 and GSTT1 polymorphism. Anal Biochem 236:184–186

    Article  PubMed  CAS  Google Scholar 

  2. Barnes PJ (1990) Reactive oxygen species and airway inflammation. Free Radic Biol Med 9:235–243

    Article  PubMed  CAS  Google Scholar 

  3. Brasch-Andersen C, Christiansen L, Tan Q et al (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

    Article  PubMed  CAS  Google Scholar 

  4. Carroll WD, Lenney W, Jones PW (2005) Effects of glutathione S-transferase M1, T1, and P1 on lung function in asthmatic families. Clin Exp Allergy 35:1155–1161

    Article  PubMed  CAS  Google Scholar 

  5. Ebrahimi M, Podolskaya SV, Gorovenko NG (2004) Genetic polymorphisms of glutathione S-transferase mu1 (GSTM1) and theta1 (GSTT1) and bronchial asthma susceptibility in Ukrainian population. Iran J Biotechnol 2:230–235

    CAS  Google Scholar 

  6. Gilliland FD, Rappaport EB, Berhane K et al (2002) Effects of glutathione S-transferase P1, M1, T1 on acute respiratory illness in school children. Am J Respir Crit Care Med 166:346–351

    Article  PubMed  Google Scholar 

  7. Hanene C, Jihene L, Jamel A et al (2007) Association of GST genes polymorphisms with asthma in Tunisian children. Mediators Inflamm 2007:19564

    Article  PubMed  Google Scholar 

  8. Hayes JD, Strange RC (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 62:154–166

    Article  Google Scholar 

  9. Henderson AJ, Newson RB, Rose-Zerilli M et al (2010) Maternal Nrf2 and gluthathione-S-transferase polymorphisms do not modify associations of prenatal tobacco smoke exposure with asthma and lung function in school-aged children. Thorax 65:897–902

    Article  PubMed  CAS  Google Scholar 

  10. Holla LI, Stejskalova A, Vasku A (2006) Polymorphisms of the GSTM1 and GSTT1 genes in patients with allergic diseases in the Czech population. Allergy 61:265–267

    Article  PubMed  CAS  Google Scholar 

  11. Imboden M, Rochat T, Brutsche MH et al (2008) Glutathione S-transferase genotype increases risk of progression from bronchial hyperresponsiveness to asthma in adults. Thorax 63:322–328

    Article  PubMed  CAS  Google Scholar 

  12. Islam T, Berhane K, McConnell R (2009) Glutathione-S-transferase (GST) P1, GSTM1, exercise, ozone and asthma incidence in school children. Thorax 64:197–202

    Article  PubMed  CAS  Google Scholar 

  13. Ivaschenko TE, Sideleva OG, Baranov VS (2002) Glutathione S-transferase micro and theta gene polymorphisms as new risk factors of atopic bronchial asthma. J Mol Med 80:39–43

    Article  PubMed  CAS  Google Scholar 

  14. Janeric S, Gunilla E (1997) The role of human glutathione transferases and epoxide hydrolases in the metabolism xenobiotics. Environ Health Perspect 105:791–799

    Google Scholar 

  15. Kallenbach J, Baynes R, Fine B et al (1992) Persistent neutrophil activation in mild asthma. J Allergy Clin Immunol 90:272–274

    Article  PubMed  CAS  Google Scholar 

  16. Kay AB (1991) Asthma and inflammation. J Allergy Clin Immunol 87:893–910

    Article  PubMed  CAS  Google Scholar 

  17. Lima CSP, Neri IA, Lourenco GJ et al (2010) Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genetic polymorphisms and atopic asthma in children from Southeastern Brazil. Genet Mol Biol 33:438–441

    Article  PubMed  CAS  Google Scholar 

  18. London SJ (2007) Gene–air pollution interactions in asthma. Proc Am Thorac Soc 4:217–220

    Article  PubMed  CAS  Google Scholar 

  19. Mak JC, Leung HC, Ho SP et al (2004) Systemic oxidative and antioxidative status in Chinese patients with asthma. J Allergy Clin Immunol 114:260–264

    Article  PubMed  CAS  Google Scholar 

  20. Piacentini S, Polimanti R, Moscatelli B et al (2010) Glutathione S-transferase gene polymorphisms and air pollution as interactive risk factors for asthma in a multicentre Italian field study: a preliminary study. Ann Hum Biol 37:427–439

    Article  PubMed  CAS  Google Scholar 

  21. Romieu I, Sienra-Monge JJ, Ramirez-Aguilar M et al (2004) Genetic polymorphism of GSTM1 and antioxidant supplementation influence lung function in relation to ozone exposure in asthmatic children in Mexico City. Thorax 59:8–10

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  23. Shaheen SO, Newson RB, Ring SM et al (2010) Prenatal and infant acetaminophen exposure, antioxidant gene polymorphisms, and childhood asthma. J Allergy Clin Immunol 126:1141–1148

    Article  PubMed  CAS  Google Scholar 

  24. Tamer L, Calikoglu M, Ates NA et al (2004) Gutathione-S-transferase gene polymorphisms (GSTT1, GSTM1, and GSTP1) as increased risk factors for asthma. Respirology 9:493–498

    Article  PubMed  Google Scholar 

  25. Watson MA, Stewart RK, Smith GBJ 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 

  26. Weiss ST (1997) Diet as a risk factor for asthma. Ciba Found Symp 206:244–257

    PubMed  CAS  Google Scholar 

  27. Xu J, Turner A, Little J et al (2002) Positive results in association studies are associated with departure from Hardy–Weinberg equilibrium: hint for genotyping error? Hum Genet 111:573–574

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

J. Singh is thankful to the University Grants Commission, New Delhi, India, for providing grant support for the study [UGC Grant F.No. 40-161/2011 (SR)]. It is submitted that the University Grants Commission, New Delhi, India, is a government organization that funds studies in the universities across the country to promote research and is not affected by the outcomes of this manuscript in any way.

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Biotechnology, Panjab University, Chandigarh, India

    Niti Birbian, Jagtar Singh & Neha Singla

  2. Department of Pulmonary Medicine, PGIMER, Chandigarh, India

    Surinder Kumar Jindal

  3. Department of Biotechnology, S.G.G.S. College, Chandigarh, India

    Amit Joshi

  4. Department of Biotechnology, G.G.D.S.D. College, Chandigarh, India

    Navneet Batra

Authors
  1. Niti Birbian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jagtar Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Surinder Kumar Jindal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amit Joshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Navneet Batra
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Neha Singla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jagtar Singh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Birbian, N., Singh, J., Jindal, S.K. et al. GSTT1 and GSTM1 Gene Polymorphisms as Major Risk Factors for Asthma in a North Indian Population. Lung 190, 505–512 (2012). https://doi.org/10.1007/s00408-012-9385-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-012-9385-9

Keywords

Search

Navigation