Human cytochrome P4502E1 (CYP2E1) is a well-conserved xenobiotic-metabolizing enzyme expressed inliver, kidney, nasal mucosa, brain, lung, and other tissues. CYP2E1 is inducible by ethanol, acetone, and otherlow-molecular weight substrates and may mediate development of chemically-mediated cancers. CYP2E1polymorphisms alter the transcriptional activity of the gene. This study was conducted in order to investigatethe allele frequency variation in different populations of Andhra Pradesh. Two hundred and twelve subjectsbelonging to six populations were studied. Genotype and allele frequency were assessed through TaqMan allelicdiscrimination (rs6413419) and polymerase chain reaction-sequencing (-1295G>C and -1055C>T) after DNAisolation from peripheral leukocytes. The data were compared with other available world populations. The SNPrs6413419 is monomorphic in the present study, -1295G>C and -1055C>T are less polymorphic and followedHardy-Weinberg equilibrium in all the populations studied. The -1295G>C and -1055C>T frequencies were similarand acted as surrogates in all the populations. Analysis of HapMap populations data revealed no significant LDbetween these markers in all the populations. Low frequency of CYP2E1*c2 could be useful in the understandingof south Indian population gene composition, alcohol metabolism, and alcoholic liver disease development.However, screening of additional populations and further association studies are necessary. The heterogeneityof Indian population as evidenced by the different distribution of CYP2E1*c2 may help in understanding thepopulation genetic and evolutionary aspects of this gene.