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

Abstract

ABSTRACT. 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 (3ꞌUTR) 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>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, 6455©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 12 (4): 6454-6461 (2013) UGT1A9, 1A7, and 1A1 genetic polymorphism 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.

Comparison of UGT1A1 Polymorphism as Guidance of Irinotecan Dose Escalation in RAS Wild-Type Metastatic Colorectal Cancer Patients Treated With Cetuximab or Bevacizumab Plus FOLFIRI as the First-Line Therapy

“…UGT1A1 gene polymorphism is differently distributed among different ethnicities, which may lead to various toxicity and efficacies of irinotecan 8 . Even with the same ethnicity, the gene frequency differs in varying geographical regions 9 . The recommended irinotecan dose in FOLFIRI (leucovorin + fluorouracil + irinotecan) is 180 mg/m 2 based on a dose-finding study 10 .…”

Bilirubin metabolism andUDP‐glucuronosyltransferase1A1variants in Asians: Pathogenic implications and therapeutic response

“…A total of 66 studies published until December 31, 2021, met the inclusion criteria and were included in this review. Of the 66 studies, 20 included Chinese populations [5][6][7][8][9][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] (two studies also included Chinese Tibetan individuals 9,22 ), 4 included Indian populations, 19,37-39 2 included Indonesian populations, 14,40 12 included Japanese populations 4,10,20,[41][42][43][44][45][46][47][48][49] (one study also included individuals from Uzbekistan 20 ), 4 included Korean populations, 11,12,50,51 3 included Malaysian populations, 15,16,52 1 included Saudi individuals, 21 18 included Taiwanese individuals, 1,3,13,[53][54][55]…”

Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer: a study from Guangxi Zhuang

“…Studies have shown that UGT1A1 gene polymorphism is differently distributed among different ethnicities, which may lead to different toxicities and efficacies of irinotecan [6]. Even with the same ethnicity, the gene frequency differs in varying geographical regions [7]. Moreover, the frequency of gene mutation differs among various ethnic groups due to different genetic backgrounds.…”