Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research
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Year : 2012  |  Volume : 136  |  Issue : 2  |  Page : 249-259

Polymorphisms of UGT1A1*6, UGT1A1*27 & UGT1A1*28 in three major ethnic groups from Malaysia

1 Pharmacogenomics Centre (PROMISE), Faculty of Pharmacy, Universiti Teknologi MARA, Selangor, Malaysia
2 Pharmacogenomics Centre (PROMISE), Faculty of Pharmacy, Universiti Teknologi MARA; Department of Biomedical Science, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia

Correspondence Address:
M Z Salleh
Head, Pharmacogenomics Centre (PROMISE), Faculty of Pharmacy, Universiti Teknologi MARA 42300 Puncak Alam, Selangor DE
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Source of Support: None, Conflict of Interest: None

PMID: 22960892

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Background & objectives: Genetic polymorphisms of uridine diphosphate glucuronyltransferase 1A1 (UGT1A1) have been associated with a wide variation of responses among patients prescribed with irinotecan. Lack of this enzyme is known to be associated with a high incidence of severe toxicity. The objective of this study was to investigate the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28), which are associated with reduced enzyme activity and increased irinotecan toxicity, in the three main ethnic groups in Malaysia (Malays, Chinese and Indians). Methods: A total of 306 healthy unrelated volunteers were screened for UGT1A1*28, UGT1A1*6 and UGT1A1*27. Blood samples (5 ml) were obtained from each subject and DNA was extracted. PCR based methods were designed and validated for detection of UGT1A1*6, UGT1A1*27 and UGT1A1*28. Direct DNA sequencing was performed to validate the results of randomly selected samples. Results: Malays and Indian have two-fold higher frequency of homozygous of UGT1A1*28 (7TA/7TA) which was 8 and 8.8 per cent, respectively compared to the Chinese (4.9%). However, the distribution of UGT1A1*6 and UGT1A1*27 showed no significant differences among them. UGT1A1*27 which has not been detected in Caucasian and African American population, was found in the Malaysian Malays (3.33%) and Malaysian Chinese (2.0%). Interpretation & conclusions: There was interethnic variability in the frequency of UGT1A1*28 in the Malaysian population. Our results suggest that genotyping of UGT1A1*6, UGT1A1*28 and UGT1A1*27 need to be performed before patients are prescribed with irinotecan due to their high prevalence of allelic variant which could lead to adverse drug reaction.

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