title: Polymorphisms of UGT1A1*6, UGT1A1*27 & UGT1A1*28 in three major ethnic groups from Malaysia.
abstract: OBJECTIVE
  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*, UUGT1A1*27 and UUGT1A1*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%).
  
  
  CONCLUSIONS
  There was interethnic variability in the frequency of UGT1A1*28 in the Malaysian population. Our results suggest that genotyping of UUGT1A1*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.
authors.affiliation: Pharmacogenomics Centre (PROMISE), Faculty of Pharmacy, Universiti Teknologi MARA, Selangor, Malaysia.
authors.forename: L K
authors.initials: LK
authors.lastname: Teh
authors.forename: H
authors.initials: H
authors.lastname: Hashim
authors.forename: Z A
authors.initials: ZA
authors.lastname: Zakaria
authors.forename: M Z
authors.initials: MZ
authors.lastname: Salleh
mesh_terms: D054316:Biomarkers, Pharmacological / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D014453:Glucuronosyltransferase / Q000097:blood / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008296:Malaysia; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D000099148:UGT1A1 Enzyme
chemical_list: D054316:Biomarkers, Pharmacological; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme