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. 2012 Apr;13(5):555-70.
doi: 10.2217/pgs.11.160.

Worldwide variation in human drug-metabolism enzyme genes CYP2B6 and UGT2B7: implications for HIV/AIDS treatment

Jing Li  1 , Vincent Menard, Rebekah L Benish, Richard J Jurevic, Chantal Guillemette, Mark Stoneking, Peter A Zimmerman, Rajeev K Mehlotra
Affiliations

Worldwide variation in human drug-metabolism enzyme genes CYP2B6 and UGT2B7: implications for HIV/AIDS treatment

Jing Li et al. Pharmacogenomics. 2012 Apr.

Abstract

Aim: Hepatic enzymes, CYP2B6 and UGT2B7 play a major role in the metabolism of the widely used antiretroviral drugs efavirenz, nevirapine and zidovudine. In the present study, we provide a view of UGT2B7 haplotype structure, and quantify the genetic diversity and differentiation at both CYP2B6 and UGT2B7 genes on a worldwide scale.

Materials & methods: We genotyped one intronic and three promoter SNPs, and together with three nonsynonymous SNPs, inferred UGT2B7 alleles in north American (n = 326), west African (n = 133) and Papua New Guinean (n = 142) populations. We also included genotype data for five CYP2B6 and six UGT2B7 SNPs from an additional 12 worldwide populations (n = 629) analyzed in the 1000 Genomes Project.

Results: We observed significant differences in certain SNP and allele frequencies of CYP2B6 and UGT2B7 among worldwide populations. Diversity values were higher for UGT2B7 than for CYP2B6, although there was more diversity between populations for CYP2B6. For both genes, most of the genetic variation was observed among individuals within populations, with the Papua New Guinean population showing the highest pairwise differentiation values for CYP2B6, and the Asian and European populations showing higher pairwise differentiation values for UGT2B7.

Conclusion: These new genetic distinctions provide additional insights for investigating differences in antiretroviral pharmacokinetics and therapy outcomes among ethnically and geographically diverse populations.

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Figures

Figure 1
Figure 1. CYP2B6 and UGT2B7 haplotype diversity in various populations
Details regarding the study (EA, AFA, ASA, HA, west African and PNG) and the reference (CEU, TSI, GBR, FIN, ASW, YRI, LWK, CHB, CHS, JPT, MXL and PUR) populations are provided in supplementary table s1 and in the ‘Materials and methods’ section. AFA: African–American; ASA: Asian–American; ASW: African ancestry from southwest USA; CEU: Northern and western European from UT, USA; CHB: Han Chinese from Beijing, China; CHS: Han Chinese from south China; EA: European–American; FIN: Finnish; HA: Hispanic–American; JPT: Japanese from Tokyo, Japan; LWK: Luhya from Webuye, Kenya; MXL: Mexican ancestry from Los Angeles, CA, USA; PNG: Papua New Guinean; PUR: Puerto Rican from Puerto Rico, USA; TSI: Toscani from Italy; YRI: Yoruba from Ibadan, Nigeria.
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References

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Websites

    1. WHO HIV/AIDS Antiretroviral therapy. www.who.int/hiv/topics/treatment/en/index.html.
    1. CYP2B6 allele nomenclature. www.cypalleles.ki.se/cyp2b6.htm.
    1. UGT2B7 allele nomenclature. www.pharmacogenomics.pha.ulaval.ca/webdav/site/pharmacogenomics/shared/N....
    1. BEAGLE Genetic Analysis Software Package. faculty.washington.edu/browning/beagle/beagle.html.
    1. GENEPOP www.genepop.curtin.edu.au/

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