Abstract
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.
Highlights
Drug metabolizing enzymes are involved in the processing of xenobiotics to expel them from the body and occasionally they mediate the toxicity or carcinogenicity through the metabolic activation of procarcinogens
Human cytochrome P4502E1 (CYP2E1) is a well-conserved xenobiotic-metabolizing enzyme expressed in liver, kidney, nasal mucosa, brain, lung, and other tissues
Low frequency of CYP2E1*c2 could be useful in the understanding of south Indian population gene composition, alcohol metabolism, and alcoholic liver disease development
Summary
Drug metabolizing enzymes are involved in the processing of xenobiotics to expel them from the body and occasionally they mediate the toxicity or carcinogenicity through the metabolic activation of procarcinogens. Since the bioactivation of carcinogens through CYP is the first step of crucial importance to the cancer development, a large number of studies have been carried out to investigate the association between the CYP2E1 polymorphisms and risk of various cancers, but findings have been inconsistent (Klinchid et al, 2009; Hata et al, 2010; Wang et al, 2010; Ye et al, 2010; Balaji et al, 2011; Sameer et al, 2011). The gene spans over 11 kb and contains 9 exons coding for a membrane-bound protein consisting of 493 amino acid residues with a molecular weight of ~ 57 kDa (Lewis et al, 1997) Both the 5’-flanking region (5’-FR) and 3’-untranslated-region (3’-UTR) harbour several mutations known to alter the transcriptional activity of the gene (Hayashi et al, 1991; Chen et al, 2006). V179I (dbSNP rs6413419), -1295G>C (dbSNP rs3813867) and -1055C>T (dbSNP rs2031920) in 5’-flanking region and T7678A polymorphism in intron 6, were investigated in six south Indian populations
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