Functional PstI/RsaI Polymorphisms in the CYP2E1 Gene among South Indian Populations

  • Published : 2013.01.31


Human cytochrome P4502E1 (CYP2E1) is a well-conserved xenobiotic-metabolizing enzyme expressed in liver, kidney, nasal mucosa, brain, lung, and other tissues. CYP2E1 is inducible by ethanol, acetone, and other low-molecular weight substrates and may mediate development of chemically-mediated cancers. CYP2E1 polymorphisms alter the transcriptional activity of the gene. This study was conducted in order to investigate the allele frequency variation in different populations of Andhra Pradesh. Two hundred and twelve subjects belonging to six populations were studied. Genotype and allele frequency were assessed through TaqMan allelic discrimination (rs6413419) and polymerase chain reaction-sequencing (-1295G>C and -1055C>T) after DNA isolation from peripheral leukocytes. The data were compared with other available world populations. The SNP rs6413419 is monomorphic in the present study, -1295G>C and -1055C>T are less polymorphic and followed Hardy-Weinberg equilibrium in all the populations studied. The -1295G>C and -1055C>T frequencies were similar and acted as surrogates in all the populations. Analysis of HapMap populations data revealed no significant LD between these markers in all the populations. Low frequency of $CYP2E1^*c2$ could be useful in the understanding of south Indian population gene composition, alcohol metabolism, and alcoholic liver disease development. However, screening of additional populations and further association studies are necessary. The heterogeneity of Indian population as evidenced by the different distribution of $CYP2E1^*c2$ may help in understanding the population genetic and evolutionary aspects of this gene.


  1. Mendoza-Cantu A, Castorena-Torres F, Bermudez M, et al (2004). Genotype and allele frequencies of polymorphic cytochromes P450 CYP1A2 and CYP2E1 in Mexicans. Cell Biochem Funct, 22, 29-34.
  2. Omer B, Ozbek U, Akkose A, et al (2001). Genetic polymorphism of cytochrome P450 2E1 in the Turkish population. Cell Biochem Funct, 19, 273-5.
  3. Rossini A, Lima SS, Rapozo DC, et al (2006). CYP2A6 and CYP2E1 polymorphisms in a Brazilian population living in Rio de Janeiro. Braz J Med Biol Res, 39,195-201.
  4. Sambrook J, Fitsch EF, Maniatis T (1989). Molecular cloning: a laboratory manual. Cold Spring Harbor: Cold Spring Harbor Press.
  5. Sameer AS, Nissar S, Qadri Q, et al (2011). Role of CYP2E1 genotypes in susceptibility to colorectal cancer in the Kashmiri population. Hum Genomics, 5, 530-7.
  6. Schneider S, Roessli D, Excoffier L (2000). Arlequin v.2.0: a software for population genetics data analysis. Geneva, Switzerland: Genetics and Biometry Laboratory, University of Geneva.
  7. Shukoor MI, Tiwari S, Sankpal UT, et al (2012). Tolfenamic acid suppresses cytochrome P450 2E1 expression in mouse liver. Integr Biol (Camb), 4, 1122-9.
  8. Sikdar N, Mahmud SA, Paul RR, et al (2003). Polymorphism in CYP1A1 and CYP2E1 genes and susceptibility to leukoplakia in Indian tobacco users. Cancer Lett, 195, 33-42.
  9. Sohda T, Shimizu M, Kamimura S, et al (1993). Immunohistochemical demonstration of ethanol-inducible P450 2E1 in rat brain. Alcohol Suppl, 1, 69-75.
  10. Tanaka T (2009). HapMap project. Nihon Rinsho, 67, 1068-71.
  11. Tang K, Li Y, Zhang Z, et al (2010). The PstI/RsaI and DraI polymorphisms of CYP2E1 and head and neck cancer risk: a meta-analysis based on 21 case-control studies. BMC Cancer, 10, 575.
  12. Ulusoy G, Arinc E, Adali O (2007). Genotype and allele frequencies of polymorphic CYP2E1 in the Turkish population. Arch Toxicol, 81, 711-8.
  13. Wang Y, Yang H, Li L, et al (2010). Association between CYP2E1 genetic polymorphisms and lung cancer risk: a meta-analysis. Eur J Cancer, 46, 758-64.
  14. Watanabe J, Hayashi S, Kawajiri K (1994). Different regulation and expression of the human CYP2E1 gene due to the RsaI polymorphism in the 5'-flanking region. J Biochem, 116, 321-6.
  15. Ye X, Peng T, Liu T, et al (2010). Association between aldehyde dehydrogenase-2/cytochrome P450 2E1 genetic polymorphism and habit of alcohol drinking and the susceptibility of hepatocellular carcinoma. Wei Sheng Yan Jiu, 39, 42-5.
  16. Chen JM, Ferec C, Cooper DN (2006). A systematic analysis of disease-associated variants in the 3' regulatory regions of human protein-coding genes I: general principles and overview. Hum Genet, 120, 1-21.
  17. Cubells JF, Kobayashi K, Nagatsu T, et al (1997). Population genetics of a functional variant of the dopamine betahydroxylase gene (DBH). Am J Med Genet, 74, 374-9.<374::AID-AJMG7>3.0.CO;2-P
  18. Evans WE, Relling MV (1999). Pharmacogenomics: translating functional genomics into rational therapeutics. Science, 286, 487-91.
  19. Garte S, Gaspari L, Alexandrie AK, et al (2001). Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev, 10, 1239-48.
  20. Gattas GJ, de Carvalho MB, Siraque MS, et al (2006). Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 associated with head and neck cancer. Head Neck, 28,819-26.
  21. Gonzalez FJ (2007). The 2006 bernard B. brodie award lecture. Cyp2e1. Drug Metab Dispos, 35, 1-8.
  22. Hata S, Miki Y, Fujishima F, et al (2010). Cytochrome 3A and 2E1 in human liver tissue: Individual variations among normal Japanese subjects. Life Sci, 86, 393-401.
  23. Hayashi S, Watanabe J, Kawajiri K (1991). Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem, 110, 559-65.
  24. Klinchid J, Chewaskulyoung B, Saeteng S, et al (2009). Effect of combined genetic polymorphisms on lung cancer risk in northern Thai women. Cancer Genet Cytogenet, 195, 143-9.
  25. Korytina GF, Kochetova OV, Akhmadishina LZ, et al (2012). Polymorphisms of cytochrome P450 Genes in three ethnic groups from Russia. Balkan Med J, 29, 252-60.
  26. Krishnakumar D, Gurusamy U, Dhandapani K, et al (2012). Genetic polymorphisms of drug-metabolizing phase I enzymes CYP2E1, CYP2A6 and CYP3A5 in South Indian population. Fundam Clin Pharmacol, 26, 295-306.
  27. Lee MY, Mukherjee N, Pakstis AJ, et al (2008). Global patterns of variation in allele and haplotype frequencies and linkage disequilibrium across the CYP2E1 gene. Pharmacogenomics J, 8, 349-56.
  28. Lewis DF, Bird MG, Parke DV (1997). Molecular modelling of CYP2E1 enzymes from rat, mouse and man: an explanation for species differences in butadiene metabolism and potential carcinogenicity, and rationalization of CYP2E substrate specificity. Toxicology, 118, 93-113.
  29. Matthias C, Jahnke V, Fryer AA, et al (2002). Influence of glutathione s-transferase and cytochrome p450 polymorphisms on prognosis of head and neck cancer. Laryngorhinootologie, 81, 406-12.
  30. Balaji L, Singh KB, Bhaskar LV (2011). Genetic polymorphisms of the CYP2E1 gene do not contribute to oral cancer susceptibility in south Indians. Asian Pac J Cancer Prev, 12, 1523-7.
  31. Barrett JC, Fry B, Maller J, et al (2005). Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics, 21, 263-5.

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