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Prevalence of UGT1A9 and UGT2B7 nonsynonymous single nucleotide polymorphisms in West African, Papua New Guinean, and North American populations

  • Pharmacogenetics
  • Published:
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Abstract

Objective

UDP-glucuronosyltransferases (UGTs) UGT1A9 and UGT2B7 are involved in the metabolism of antimalarial dihydroartemisinin and antiretroviral zidovudine. Our aim was to analyze the prevalence of UGT1A9 (chromosome 2) and UGT2B7 (chromosome 4) nonsynonymous single nucleotide polymorphisms (SNPs) in West African (WA), Papua New Guinean (PNG), and North American (NA) populations.

Methods

Using a post-PCR ligation detection reaction-fluorescent microsphere assay, frequencies of UGT1A9 (8G > A, 98T > C, 766G > A) and UGT2B7 (211G > T, 802C > T, 1192G > A) SNPs were determined in WA (n = 133, 5 countries), PNG (n = 153), and NA (n = 350, 4 ethnic groups) individuals.

Results

The UGT1A9 variant alleles were not common in the study populations. None of the SNPs were present in WA and PNG. Among NA, all 3 SNPs were present (1% each) in Asian-Americans, while 98T > C was present only in Caucasian-Americans (1%) and Hispanic-Americans (1%). Regarding UGT2B7 SNPs, the prevalence of 802C > T was 21% in WA, 28% in PNG, and 28–52% in NA. The SNP 211G > T was present only in Asian-Americans (9%) and Hispanic-Americans (2%), while 1192G > A was not present in any of the subjects. No significant linkage was observed at UGT1A9, UGT2B7, and between both the loci in any of the study populations.

Conclusions

Taken together, the UGT1A9-UGT2B7 polymorphism profile in WA and PNG populations is similar to African-Americans, but different from Asian-Americans. It is important to determine if these differences, along with previously reported differences in cytochrome P450 2B6 allele frequencies, are associated with altered metabolism/effectiveness of artemisinin drugs.

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Acknowledgements

We are grateful to Dr. Chantal Guillemette, Dr. Robert Salata, Dr. Charles King, Dr. Carolyn Myers, Mr. David McNamara, and Ms. Jacquelyn Bales for their comments on the manuscript. Thanks are due to Mr. Mark Ziats for his help during the early stages of this work, and to Ms. Melinda Blood for her excellent technical assistance in extracting genomic DNA from blood samples. This work was supported by grants (AI-52312) from National Institutes of Health and the James B. Pendleton Charitable Trust to PAZ. R.K.M. was supported by Fogarty International Center and in part by a grant (AI-36478) from National Institutes of Health. The experiments comply with the current laws, inclusive of ethics approval, of the United States of America.

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Authors and Affiliations

  1. Center for Global Health and Diseases, Case Western Reserve University, School of Medicine, Wolstein Research Building #4204, 2103 Cornell Road, Cleveland, OH, 44106-7286, USA

    Rajeev K. Mehlotra & Peter A. Zimmerman

  2. Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

    Moses J. Bockarie

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  1. Rajeev K. Mehlotra
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  2. Moses J. Bockarie
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  3. Peter A. Zimmerman
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Correspondence to Rajeev K. Mehlotra.

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Table 1

UGT1A9 and UGT2B7 PCR primers and amplifications conditions (PDF 58 kb)

Table 2

LDR primers and microspheres to detect UGT1A9 and UGT2B7 polymorphisms (PDF 53 kb)

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Mehlotra, R.K., Bockarie, M.J. & Zimmerman, P.A. Prevalence of UGT1A9 and UGT2B7 nonsynonymous single nucleotide polymorphisms in West African, Papua New Guinean, and North American populations. Eur J Clin Pharmacol 63, 1–8 (2007). https://doi.org/10.1007/s00228-006-0206-z

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