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As part of a series of pharmacogenomics studies of the Chinese population, we investigated genetic polymorphisms of some UGT1A regions. The three genes that were analyzed were UGT1A9, 1A7, and 1A1; we sequenced their exons, together with promoters, surrounding introns and 3'-untranslated regions (3'UTR) in 100 unrelated-healthy Chinese Tibetan individuals. We compared the data with information on Han Chinese of the same region, which we downloaded from the HapMap database. We identified 40 polymorphisms; 16 of them were shared by the two populations. We then analyzed their linkage disequilibrium map. The UGT1As cluster can be divided into two linkage blocks in the Tibetan population: Block 1 (UGT1A9, UGT1A7), Block 2 (3'-UTR). Furthermore, we identified haplotypes and selected their tagSNPs. In exon 1 of UGT1A7 gene, 393G&gt;A (Arg131Gln, rs17868324) was found at a frequency of 44.4% in the Tibetan population, compared to only 0.7% in the Han population. The linkage blocks in the Han Chinese sample differed from that of the Chinese Tibetan group; the former had Block 1 (UGT1A9, UGT1A7), Block 2 (UGT1A7), and Block 3 (3'-UTR). These findings provide fundamental information for future molecular genetic studies of the UGT1A gene cluster as well as for personalized medicine in Chinese.

Differences in frequencies of UGT1A9, 1A7, and 1A1 genetic polymorphisms in Chinese Tibetan versus Han Chinese populations