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Global patterns of variation in allele and haplotype frequencies and linkage disequilibrium across the CYP2E1 gene

The Pharmacogenomics Journal volume 8, pages 349–356 (2008)Cite this article

Abstract

Cytochrome P450 2E1, gene symbol CYP2E1, is one of a family of enzymes with a central role in activating and detoxifying xenobiotics and endogenous compounds. Genetic variation at this gene has been reported in different human populations, and some association studies have reported increased risk for cancers and other diseases. To the best of our knowledge, multi-single-nucleotide polymorphism haplotypes and linkage disequilibrium (LD) have not been systematically studied for CYP2E1 in multiple populations. Haplotypes can greatly increase the power both to identify patterns of genetic variation relevant for gene expression as well as to detect disease-related susceptibility mutations. We present frequency and LD data and analyses for 11 polymorphisms and their haplotypes that we have studied on over 2600 individuals from 50 human population samples representing the major geographical regions of the world. The diverse patterns of haplotype variation found in the different populations we have studied show that ethnicity may be an important variable helping to explain inconsistencies that have been reported by association studies. More studies clearly are needed of the variants we have studied, especially those in the 5′ region, such as the variable number of tandem repeats, as well as studies of additional polymorphisms known for this gene to establish evidence relating any systematic differences in gene expression that exist to the haplotypes at this gene.

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Abbreviations

CYP2E1 :

cytochrome P450, family 2, subfamily E, polypeptide 1

LD:

linkage disequilibrium

PCR:

polymerase chain reaction

SNP:

single-nucleotide polymorphism

UID:

unique identifier

VNTR:

variable number of tandem repeats

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Acknowledgements

This work was funded, in part, by National Institute of Health grants GM057672 and AA009379 to Kenneth K Kidd. None of the authors has any conflicts of interest related to the data presented here. We thank all the colleagues who helped us assemble the population samples. Special thanks are due the many hundreds of individuals from these populations who volunteered to give blood samples for studies such as this.

Author information

Authors and Affiliations

  1. Department of Genetics, Yale University School of Medicine, New Haven, CT, USA

    M-Y Lee, N Mukherjee, A J Pakstis, W C Speed, J R Kidd & K K Kidd

  2. Department of Preventive Medicine, School of Medicine, Keimyung University, Daegu, Republic of Korea

    M-Y Lee

  3. Institute of Biotechnology and Genetic Engineering, University of Karachi, Karachi, Pakistan

    S Khaliq, A Mohyuddin & S Q Mehdi

Authors
  1. M-Y Lee
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  2. N Mukherjee
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  7. W C Speed
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Correspondence to K K Kidd.

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None declared.

Electronic databases cited

ALFRED, The ALlele FREquency Databse; http://alfred.med.yale.edu; PharmGKB, The Pharmacogenetics and Pharmacogenomics Knowledge Base, http://www.PharmGKB.org

Supplementary Information accompanies the paper on the The Pharmacogenomics Journal Web site (http://www.nature.com/tpj)

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Lee, MY., Mukherjee, N., Pakstis, A. et al. Global patterns of variation in allele and haplotype frequencies and linkage disequilibrium across the CYP2E1 gene. Pharmacogenomics J 8, 349–356 (2008). https://doi.org/10.1038/tpj.2008.9

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