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Prevalence of the UGT1A1*6 (c.211G>A) polymorphism and irinotecan toxicity in Iranian populations of different ethnicities

Background: Pharmacogenetic studies on irinotecan treatment in patients with metastatic colorectal cancer have indicated that genetic polymorphisms in UGT1A1*6 can lead to decreased enzyme activity and accumulation of the toxic metabolite SN-38. Here, we compared the prevalence of UGT1A1*6 in an Ira...

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Main Authors: Shakibi, Reyhaneh, Kamalidehghan, Behnam, Ahmadipour, Fatemeh, Meng, Goh Yong, Houshmand, Massoud
Format: Article
Language:English
Published: Karger Publishers 2015
Online Access:http://psasir.upm.edu.my/id/eprint/45994/1/Prevalence%20of%20the%20UGT1A16%20%28c.211GA%29%20polymorphism%20and%20irinotecan%20toxicity%20in%20Iranian%20populations%20of%20different%20ethnicities.pdf
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spelling oai:psasir.upm.edu.my:45994 http://psasir.upm.edu.my/id/eprint/45994/ Prevalence of the UGT1A1*6 (c.211G>A) polymorphism and irinotecan toxicity in Iranian populations of different ethnicities Shakibi, Reyhaneh Kamalidehghan, Behnam Ahmadipour, Fatemeh Meng, Goh Yong Houshmand, Massoud Background: Pharmacogenetic studies on irinotecan treatment in patients with metastatic colorectal cancer have indicated that genetic polymorphisms in UGT1A1*6 can lead to decreased enzyme activity and accumulation of the toxic metabolite SN-38. Here, we compared the prevalence of UGT1A1*6 in an Iranian population of different ethnicities with those of other populations. Materials and Methods: A total of 300 healthy people of different ethnic groups including Persian, Azari, Lure, Kurdish, Arab, Baluch and Caspian in the Iranian population were enrolled. Genotyping of the UGT1A1*6 alleles (G/G, A/G, A/A) was performed by polymerase chain reaction-restriction fragment length polymorphism and direct genomic DNA sequencing. Result: The most predictive genotype among the Iranian ethnic groups, especially Persian, was the G/G genotype (wild-type genotype). The frequency of the A/G genotype among the Persian, Azari, Lure, Kurdish, Arab, Baluch and Caspian ethnicities were 15.69% (n = 27), 11.11% (n = 8), 5.88% (n = 1), 9.09% (n = 1), 10% (n = 1), 20% (n = 1) and 0% (n = 0), respectively. Only one person with Persian ethnicity was homozygous for the mutation in UGT1A1*6 (0.58%). Additionally, the frequency of the A and G alleles in Iranians was 6.83 and 93.16%, respectively. Conclusion: The identification of the UGT1A1*6 alleles is necessary among the different Iranian ethnic groups before irinotecan therapy, suggesting that genotyping would be helpful for clinicians to optimize chemotherapy or identify individuals at risk of adverse drug reactions before clinical trials. Karger Publishers 2015 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/45994/1/Prevalence%20of%20the%20UGT1A16%20%28c.211GA%29%20polymorphism%20and%20irinotecan%20toxicity%20in%20Iranian%20populations%20of%20different%20ethnicities.pdf Shakibi, Reyhaneh and Kamalidehghan, Behnam and Ahmadipour, Fatemeh and Meng, Goh Yong and Houshmand, Massoud (2015) Prevalence of the UGT1A1*6 (c.211G>A) polymorphism and irinotecan toxicity in Iranian populations of different ethnicities. Chemotherapy, 60 (5). pp. 279-287. ISSN 0009-3157; ESSN: 1421-9794 https://www.karger.com/Article/FullText/376568 10.1159/000376568
institution UPM IR
collection UPM IR
language English
description Background: Pharmacogenetic studies on irinotecan treatment in patients with metastatic colorectal cancer have indicated that genetic polymorphisms in UGT1A1*6 can lead to decreased enzyme activity and accumulation of the toxic metabolite SN-38. Here, we compared the prevalence of UGT1A1*6 in an Iranian population of different ethnicities with those of other populations. Materials and Methods: A total of 300 healthy people of different ethnic groups including Persian, Azari, Lure, Kurdish, Arab, Baluch and Caspian in the Iranian population were enrolled. Genotyping of the UGT1A1*6 alleles (G/G, A/G, A/A) was performed by polymerase chain reaction-restriction fragment length polymorphism and direct genomic DNA sequencing. Result: The most predictive genotype among the Iranian ethnic groups, especially Persian, was the G/G genotype (wild-type genotype). The frequency of the A/G genotype among the Persian, Azari, Lure, Kurdish, Arab, Baluch and Caspian ethnicities were 15.69% (n = 27), 11.11% (n = 8), 5.88% (n = 1), 9.09% (n = 1), 10% (n = 1), 20% (n = 1) and 0% (n = 0), respectively. Only one person with Persian ethnicity was homozygous for the mutation in UGT1A1*6 (0.58%). Additionally, the frequency of the A and G alleles in Iranians was 6.83 and 93.16%, respectively. Conclusion: The identification of the UGT1A1*6 alleles is necessary among the different Iranian ethnic groups before irinotecan therapy, suggesting that genotyping would be helpful for clinicians to optimize chemotherapy or identify individuals at risk of adverse drug reactions before clinical trials.
format Article
author Shakibi, Reyhaneh
Kamalidehghan, Behnam
Ahmadipour, Fatemeh
Meng, Goh Yong
Houshmand, Massoud
spellingShingle Shakibi, Reyhaneh
Kamalidehghan, Behnam
Ahmadipour, Fatemeh
Meng, Goh Yong
Houshmand, Massoud
Prevalence of the UGT1A1*6 (c.211G>A) polymorphism and irinotecan toxicity in Iranian populations of different ethnicities
author_facet Shakibi, Reyhaneh
Kamalidehghan, Behnam
Ahmadipour, Fatemeh
Meng, Goh Yong
Houshmand, Massoud
author_sort Shakibi, Reyhaneh
title Prevalence of the UGT1A1*6 (c.211G>A) polymorphism and irinotecan toxicity in Iranian populations of different ethnicities
title_short Prevalence of the UGT1A1*6 (c.211G>A) polymorphism and irinotecan toxicity in Iranian populations of different ethnicities
title_full Prevalence of the UGT1A1*6 (c.211G>A) polymorphism and irinotecan toxicity in Iranian populations of different ethnicities
title_fullStr Prevalence of the UGT1A1*6 (c.211G>A) polymorphism and irinotecan toxicity in Iranian populations of different ethnicities
title_full_unstemmed Prevalence of the UGT1A1*6 (c.211G>A) polymorphism and irinotecan toxicity in Iranian populations of different ethnicities
title_sort prevalence of the ugt1a1*6 (c.211g>a) polymorphism and irinotecan toxicity in iranian populations of different ethnicities
publisher Karger Publishers
publishDate 2015
url http://psasir.upm.edu.my/id/eprint/45994/1/Prevalence%20of%20the%20UGT1A16%20%28c.211GA%29%20polymorphism%20and%20irinotecan%20toxicity%20in%20Iranian%20populations%20of%20different%20ethnicities.pdf
_version_ 1819296688092741632
score 13.4562235

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