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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
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Polymorphisms in the UGT1A1 gene or its promoter associated with irinotecan toxicity

Polymorphisms in the UGT1A1 gene or its promoter associated with irinotecan toxicity
Allele Nucleotide change Phenotype Population prevalence
*28 (TA)7 TAA in the promoter Poor metabolizer, significantly associated with irinotecan toxicity *28 allele commonly found in African (40%) and European (33%) ancestry, but less common in East Asian ancestry (14%)[1].
*6 c.211G>A in exon 1 Poor metabolizer, significantly associated with irinotecan toxicity *6 allele more common in East Asian ancestry (13 to 18%) than African (0 to 0.1%) or European (1 to 5%) ancestry[1,2].
*93 –3156G>A in the promoter Intermediate metabolizer; functional significance not clear, although has been associated with irinotecan toxicity[3] Commonly found in African (34%) and European (27%) ancestry; less common in East Asian ancestry (13%)[4].

UGT1A1: uridine diphospho-glucuronosyltransferase 1A1.

¶ Additional two base-pair T-A (thymine-adenine) repeat in the gene promoter, compared with wild-type UGT1A1 (*1 allele), which is (TA)6 TAA and associated with normal UGT1A1 expression and enzyme activity.
References:
  1. Palomaki GE, Bradley LA, Douglas MP, et al. Can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? An evidence-based review. Genet Med 2009; 11:21.
  2. National Center for Biotechnology Information. dbSNP:rs4148323. Available at: https://www.ncbi.nlm.nih.gov/snp/rs4148323#frequency_tab (Accessed on February 25, 2022).
  3. Innocenti F, Kroetz DL, Schuetz E, et al. Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics. J Clin Oncol 2009; 27:2604.
  4. National Center for Biotechnology Information. dbSNP:rs10929302. Available at: https://www.ncbi.nlm.nih.gov/snp/rs10929302?vertical_tab=true#frequency_tab (Accessed on February 25, 2022).
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