Diclofenac‐induced adverse drug reactions and hyperbilirubinemia caused by a variant gene

Chen, En-Sung; Lee, Chia‐Long; Tsui, Kochung; Huang, Ching‐Shan

doi:10.1002/kjm2.12472

Cited by 3 publications

(1 citation statement)

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“…For example, glucuronidation activity toward the acetaminophen of p.Phe364Leu–UGT1A1A9 was 5.0% of the wild type and glucuronidation activity toward the 2‐amino‐5‐nitro‐4‐trifluoromethylphenol (a major metabolite of flutamide) of p.Tyr486Asp‐UGT1A6 was <1% of the wild type 77,78 . Therefore, the gene analysis of variations on common exons in patients who experience adverse effects of drugs can help determine the significance of the variations 77,79 …”

Section: Variation Status Of Ugt1a1 and Diseasesmentioning

confidence: 99%

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

Huang

Chen

Huang

2022

The Kaohsiung J of Med Scie

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In the Asian general population, at least six single‐nucleotide variants (SNVs) in the UDP‐glucuronosyltransferase (UGT) 1A1 gene have been identified: −3279T>G, −53A(TA)6TAA>A(TA)7TAA, 211G>A, 686C>A, 1091C>T, and 1456T>G. Each of these six SNVs was observed in at least four ethnic groups of the 12 Asian populations studied. In East Asian populations, the descending frequency of these six SNVs was as follows: −3279G>[−53A(TA)7TAA, 211A]>(686A, 1091T)>1456G. Because of the presence of linkage disequilibrium and the expulsion phenomenon, when the SNVs −3279G, −53A(TA)7TAA, 211A, and 686A were simultaneously involved, 15 instead of the estimated 81 genotypes were observed. Those carrying 686AA or 1456GG developed Gilbert's syndrome or Crigler–Najjar syndrome type 2. Both −53A(TA)7TAA/A(TA)7TAA and 211AA are the main causes of Gilbert's syndrome in East Asian populations. In East Asian populations, the 211AA genotype is the main cause of neonatal hyperbilirubinemia, whereas −53A(TA)7TAA/A(TA)7TAA exerts a protective effect on hyperbilirubinemia development in neonates fed with breast milk. Both 211A and −53A(TA)7TAA are significantly associated with adverse drug reactions induced by irinotecan (one of the most widely used anticancer agents) in Asians. However, at least three common SNVs (−3279G, −53A(TA)7TAA, and 211A) should be comprehensively analyzed. This study investigated the clinical significance of these six SNVs and demonstrated that examining UGT1A1 variants in Asian populations is considerably challenging.

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Section: Variation Status Of Ugt1a1 and Diseasesmentioning

confidence: 99%