Abstract
Objective
To investigate the distribution of the homozygous null genotypes of GSTM1 and GSTT1 in the South Indian population.
Methods
Five hundred and seventeen unrelated natives of the South Indian states of Tamilnadu and Pondicherry (n=170), Kerala (n=122), Karnataka (n=110) and Andhra Pradesh (n=115) were analyzed for homozygous deletions of GSTM1 and GSTT1. A multiplex polymerase chain reaction method simultaneously detected both GSTM1 and GSTT1 homozygous null genotypes. The observed frequencies from the four groups were compared statistically with each other and the combined frequencies were compared with frequencies of other major populations previously reported in the literature.
Results
In South India, 30.4% (95% CI 26.4–34.3) lacked the GSTM1 gene, 16.8% (13.6–20.1) lacked the GSTT1 gene and 4.6% (3.0–6.8) lacked both the GSTM1 and GSTT1 genes. The highest frequency of GSTM1 null was observed in Karnataka (36.4%, 27.4–45.4), while Andhra Pradesh had the lowest frequency of the GSTM1 and GSTT1 combined double-null genotypes (1.7%, 0.21–6.2).
Conclusion
The prevalence of the GSTM1 null genotype differed within India. The frequency of GSTM1 null in South Indians was significantly lower than that in Caucasians. The frequencies of both GSTM1 and GSTT1 null genotypes in South Indians were significantly lower than in the Japanese.
Similar content being viewed by others
References
Ketterer B (2001) A bird’s eye view of the glutathione transferase field. Chem Biol Interact 138:27–42
Hayes JR, deBethizy JD (2001) Metabolism: a determinant of toxicity. In: Hayes AW (ed) Principles and methods of toxicology. Taylor and Francis, Philadelphia, pp 112–119
Testai E (2002) Basic aspects of toxicology: metabolic pathways and individual factors of susceptibility to xenobiotics. In: Chyczewski L, Niklinski J, Pluygers E (eds) Endocrine disrupters and carcinogenic risk assessment. IOS Press, Amsterdam, pp 255–270
Chen CL, Liu Q, Relling MV (1996) Simultaneous characterization of glutathione S-transferase M1 and T1 polymorphisms by polymerase chain reaction in American whites and blacks. Pharmacogenetics 6:187–191
Naoe T, Takeyama K, Yokozawa T, Kiyoi H, Seto M, Uike N et al (2000) Analysis of genetic polymorphism in NQO1, GST-M1, GST-T1, and CYP3A4 in 469 Japanese patients with therapy-related leukemia/myelodysplastic syndrome and de novo acute myeloid leukemia. Clin Cancer Res 6:4091–4095
Buch S, Kotekar A, Kawle D, Bhisey R (2001) Polymorphisms at CYP and GST gene loci. Prevalence in the Indian population. Eur J Clin Pharmacol 57:553–555
Sreelekha TT, Ramadas K, Pandey M, Thomas G, Nalinakumari KR, Pillai MR (2001) Genetic polymorphism of CYP1A1, GSTM1 and GSTT1 genes in Indian oral cancer. Oral Oncol 37:593–598
Roy B, Dey B, Chakraborty M, Majumder PP (1998) Frequency of homozygous null mutation at the glutathione-S-transferase M1 locus in some populations of Orissa, India. Anthropol Anz 56:43–47
Nair UJ, Nair J, Mathew B, Bartsch H (1999) Glutathione-S-transferase M1 and T1 null genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/tobacco chewers. Carcinogenesis 20:743–748
Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 74:5463–5467
Lee EJ, Wong JY, Yeoh PN, Gong NH (1995) Glutathione-S-transferase theta (GSTT1) genetic polymorphism among Chinese, Malays and Indians in Singapore. Pharmacogenetics 5:332–334
Zhao B, Lee EJ, Wong JY, Yeoh PN, Gong NH (1995) Frequency of mutant CYP1A1, NAT2 and GSTM1 alleles in normal Indians and Malays. Pharmacogenetics 5:275–280
Ismail R, The LK (2001) Genetic polymorphisms of CYP2D6: Malaysian Indians have the highest frequency for CYP2D6*4 in Asia. Eur J Clin Pharmacol 57:617–618
Adithan C, Gerard N, Naveen AT, Koumaravelou K, Shashindran CH, Krishnamoorthy R (2003) Genotype and allele frequency of CYP2D6 in Tamilian population. Eur J Clin Pharmacol 59:517–520
Adithan C, Gerard N, Vasu S, Balakrishnan R, Shashindran CH, Krishnamoorthy R (2003) Allele and genotype frequency of CYP2C9 in Tamilnadu population. Eur J Clin Pharmacol 59:707–709
Adithan C, Gerard N, Vasu S, Rosemary J, Shashindran CH, Krishnamoorthy R (2003) Allele and genotype frequency of CYP2C19 in Tamilian population. Br J Clin Pharmacol 56:331–333
Garte S, Gaspari L, Alexandrie AK, Ambrosone C, Autrup H, AutrupJL, et al (2001) Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev 10:1239–1248
Acknowledgements
The research project is funded by Indian Council of Medical research, New Delhi, India, and INSERM, Paris, France (ICMR ref. no. 50/6/2000-BMS dated 11/12/2001). We thank Mr. Sajan Jose, Kottayam for his help in sample collection of Kerala population. Technical assistance provided by Mr. R. Balakrishnan, Mr. S. Rajan and Mrs. S. Mala is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Naveen, A.T., Adithan, C., Padmaja, N. et al. Glutathione S-transferase M1 and T1 null genotype distribution in South Indians. Eur J Clin Pharmacol 60, 403–406 (2004). https://doi.org/10.1007/s00228-004-0779-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-004-0779-3