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This article is part of the supplement: Abstracts from the First International Science Symposium on HIV and Infectious Diseases (HIV SCIENCE 2012)

Open Access Oral presentation

Inter-ethnic differences in efavirenz CNS toxicity – role of cytochrome P450 2B6 polymorphisms

Lawrence S Lee1*, Gaik Hong Soon1 and Yik Ying Teo2

Author Affiliations

1 Department of Medicine, National University of Singapore, Singapore 119228, Singapore

2 Department of Statistics & Applied Probability, National University of Singapore, Singapore 117546, Singapore

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BMC Infectious Diseases 2012, 12(Suppl 1):O17  doi:10.1186/1471-2334-12-S1-O17


The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2334/12/S1/O17


Published:4 May 2012

© 2012 Lee et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Highly active antiretroviral therapy regimens that include efavirenz are effective, but adverse events are common, especially central nervous system (CNS) toxicities. We previously showed increased discontinuation rates of efavirenz due to CNS toxicities in Malay and Chinese patients in our Treat Asia HIV Observational Database (TAHOD) database. We postulate that these differences may be due to genetic differences.

Methods

We performed genome wide genotyping with the Illumina 1M and the Affymetrix 6.0 microarrays in healthy volunteers from the 3 major ethnic groups in Singapore, consisting of Chinese (mainly of southern Chinese origin), Malays and Indians (mainly of southern Indian origin). Genetic information was available from 95 Chinese, 89 Malays and 82 Indians.

Results

Allele frequencies were obtained for the rs3745274 single nucleotide polymorphism coding for the cytochrome P450 2B6 (CYP2B6) 516 G>T mutation. The allele frequency of the mutant gene was found in 22.1% in Chinese, 37.6% in Malays and 37.8% in Indians. Homozygous TT mutations were found in 4.2% in Chinese, 12.4% in Malays and 12.2% in Indians. This homozygous TT mutation frequency is higher than that found in the European American HIV-infected population, which was reported to be 3%.

Conclusion

Our study showed significant ethnic differences in CYP2B6 516 G>T mutations in Singapore. The frequencies of these mutations are significantly higher than in Caucasian populations. This finding may explain the higher discontinuation rate of efavirenz due to CNS side effects. Further studies with studying the association of CYP2B6 genotype with CNS toxicities and efavirenz concentrations are indicated.