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Interethnic differences of PEPT2 (SLC15A2) polymorphism distribution and associations with cephalexin pharmacokinetics in healthy Asian subjects

  • Pharmacogenetics
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Abstract

Objectives

The aims of this study were to characterize the population frequency of PEPT2 (SLC15A2) polymorphic variants in three Asian ethnic populations, namely Chinese, Malay and Asian Indian, and to investigate the associations of ethnicity (Chinese vs. Asian Indian), PEPT2 haplotype and cephalexin pharmacokinetics in healthy Asian subjects.

Methods

PEPT2 polymorphisms were screened from a cohort of 96 Chinese, 96 Malay and 96 Asian Indian subjects. Cephalexin (1000 mg, orally) pharmacokinetics was characterized in an additional 15 Chinese and 15 Asian Indian healthy subjects. These 30 subjects were subsequently genotyped for their PEPT2 polymorphisms.

Results

In total, ten common single nucleotide polymorphisms (SNPs) were detected in the three populations, forming two PEPT2 haplotypes. There were significant ethnic differences in PEPT2 haplotype distribution: the frequencies of the *1 and *2 alleles were 0.307 and 0.693 in the Chinese population, 0.495 and 0.505 in the Malay population and 0.729 and 0.271 in Asian Indian population, respectively. The C max of cephalexin was significantly lower in the Chinese (29.80 ± 4.09 μg ml−1) population than in the Asian Indian one (33.29 ± 4.97 μg ml−1; P = 0.045). This difference could be explained by the higher average body weight of the Chinese population. There was no other significant difference in cephalexin pharmacokinetics between either ethnic or PEPT2 genotype groups.

Conclusion

PEPT2 polymorphism distributions differ significantly between Chinese, Malay and Asian Indian populations. However, cephalexin pharmacokinetics is not meaningfully different between Chinese and Asian Indians. The association between the PEPT2 haplotype and cephalexin pharmacokinetics could not be confirmed, and future studies under better controlled conditions are needed.

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Acknowledgements

This work was supported by a grant from the National Medical Research Council, Singapore. (NMRC /1014/2005)

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Authors and Affiliations

  1. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD11, Level 5, #05–09, Clinical Research Centre, 10 Medical Drive, Singapore, 117597, Singapore

    Rui Liu, Audrey May Yi Tang, Yen Ling Tan, Lie Michael George Limenta & Edmund Jon Deoon Lee

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  1. Rui Liu
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  2. Audrey May Yi Tang
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Correspondence to Edmund Jon Deoon Lee.

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Liu, R., Tang, A.M.Y., Tan, Y.L. et al. Interethnic differences of PEPT2 (SLC15A2) polymorphism distribution and associations with cephalexin pharmacokinetics in healthy Asian subjects. Eur J Clin Pharmacol 65, 65–70 (2009). https://doi.org/10.1007/s00228-008-0488-4

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  • DOI: https://doi.org/10.1007/s00228-008-0488-4

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