Abstract
Genetic polymorphisms of UDP-glucuronosyltransferases (UGTs) are involved in individual and ethnic differences in drug metabolism. To reveal co-occurrence of the UGT1A polymorphisms, we first analyzed haplotype structures of the entire UGT1A gene complex using the polymorphisms from 196 Japanese subjects. Based on strong linkage disequilibrium between UGT1A8 and 1A10, among 1A9, 1A7, and 1A6, and between 1A3 and 1A1, the complex was divided into five blocks, Block 8/10, Block 9/6, Block 4, Block 3/1, and Block C, and the haplotypes for each block were subsequently determined/inferred. Second, using pyrosequencing or direct sequencing, additional 105 subjects were genotyped for 41 functionally tagged polymorphisms. The data from 301 subjects confirmed the robustness of block partitioning, but several linkages among the haplotypes with functional changes were found across the blocks. Thus, important haplotypes and their linkages were identified among the UGT1A gene blocks (and segments), which should be considered in pharmacogenetic studies.
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Accession codes
Abbreviations
- LD:
-
linkage disequilibrium
- PCR:
-
polymerase chain reaction
- SN-38:
-
7-ethyl-10-hydroxycamptothecin
- SNP:
-
single nucleotide polymorphism
- UGT:
-
UDP-glucuronosyltransferase
- UTR:
-
untranslated region
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Acknowledgements
This study was supported in part by the Program for Promotion of Fundamental Studies in Health Sciences and by the Health and Labour Sciences Research Grants from Ministry of Health, Labour and Welfare, and the grant from the Japan Health Sciences Foundation. We thank Ms Chie Sudo for her secretarial assistance.
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Saeki, M., Saito, Y., Jinno, H. et al. Haplotype structures of the UGT1A gene complex in a Japanese population. Pharmacogenomics J 6, 63–75 (2006). https://doi.org/10.1038/sj.tpj.6500335
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DOI: https://doi.org/10.1038/sj.tpj.6500335
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