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UGT1A1-TATA Box HRM PCR
Quantification assay of UGT1A1-TATA Box Dinucleotide Repeats cod. BM-044
Principle of the test: Quantification of UGT1A1-TATA Box Dinucleotide Repeats
Technology: High Resolution Melting Assay
Gene Target: UGT1A1 promoter
Specimen: DNA
Reporting Units: Genotype
Number of tests: 25 tests BM-044
Kit storage: -20°C
Necessary equipment: CFX96 DetectionSystem
Status: Ready to use
UGT1A1-TATA Box HRM PCR cod. BM-044
Quantification assay of UGT1A1-TATA Box Dinucleotide Repeats
· UGT1A1-TATA Box HRM PCR 25 tests BM-034
The UGT1A1-TATA Box HRM BM-034 is a research use only (RUO) assay for the evaluation of UGT1A1 gene variants.
UGT1A1 gene, coding for uridine diphosphate glucuronosyltransferase (UDP-glucuronosyltransferase, UDPGT), is an enzyme belonging to the glucuronidation pathway and responsible for the conversion of lipophilic small molecules (sterorides, bilirubin, hormones and drugs) into water-soluble metabolites.
Mutations in its promoter at the TATA Box result in the manifestation of a benign condition called Gilbert syndrome. This syndrome occurs in 8 percent of the population and is characterized by chronic nonhemolytic, unconjugated hyperbilirubinemia.
The mutation responsible for this condition results in the presence of two additional base pairs (TA) in the TATAA promoter sequence leading to 7 TA repeats (A[TA]7TAA UGT1A1*28) compared to 6 in the normal condition (UGT1A1*1) and is related to an impairment of proper messenger transcription resulting in reduced enzyme activity, proportional to the number of dinucleotide repeats.
Individuals with Gilbert syndrome are predominantly homozygous for the UGT1A1*28 allelic variant, with some cases showing the presence of the UGT1A1*37 allele, which possesses 8 dinucleotide repeats, either in homozygosity or heterozygosity with the UGT1A1*28 allele. In addition, the protein encoded by the UGT1A1 gene plays an important role in the metabolism of several drugs, such as irinotecan, belinostat, pazopanib, and nilotinib.
The chemotherapeutic drug Irinotecan, used predominantly for colorectal cancer, is one of the targets metabolized by this enzyme, but reduced metabolic activity, in individuals with UGT1A1*28 and UGT1A1*37 allelic variants, can cause toxicity with neutropenia, diarrhea, and the need for remodulation of therapy.
Reference
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2. Beutler E, Gelbart T, Demina A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8170-4.
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4. Guillemette, C., Lévesque, É. and Rouleau, M. (2014), Pharmacogenomics of Human Uridine Diphospho- Glucuronosyltransferases and Clinical Implications. Clinical Pharmacology & Therapeutics, 96: 324-339. https://doi.org/10.1038/clpt.2014.126
5. Sanchez-Dominguez CN, Gallardo-Blanco HL, Salinas-Santander MA, Ortiz-Lopez R. Uridine 5'-diphospho-glucronosyltrasferase: Its role in pharmacogenomics and human disease. Exp Ther Med. 2018 Jul;16(1):3-11. doi:10.3892/etm.2018.6184. Epub 2018 May 18. PMID: 29896223; PMCID: PMC5995049.
6. Riera P, Salazar J, Virgili AC, Tobeña M, Sebio A, Gallano P, Barnadas A, Páez D. Relevance of CYP3A4*20, UGT1A1*37 and UGT1A1*28 variants in irinotecan-induced severe toxicity. Br J Clin Pharmacol. 2018
7. Hulshof EC, Deenen MJ, Guchelaar HJ, Gelderblom H. Pre-therapeutic UGT1A1 genotyping to reduce the risk of irinotecan-induced severe toxicity: Ready for prime time. Eur J Cancer. 2020 Dec;141:9-20. doi:10.1016/j.ejca.2020.09.007. Epub 2020 Oct 23. PMID: 33125947.
8. Ehmer U, Lankisch TO, Erichsen TJ, Kalthoff S, Freiberg N, Wehmeier M, Manns MP, Strassburg CP (2008) Rapid allelic discrimination by TaqMan PCR for the detection of the Gilbert’s syndrome marker UGT1A1*28. J Mol Diagn 10(6):549–552. https://doi.org/10.2353/jmoldx.2008.080036