An Investigation Of The Genetic Polymorphisms Of N-Acetyltransferase 2 In Healthy Malays, Chinese And Indians In Malaysia And In Tuberculosis Patients On Isoniazid

N-acetyltransferases are enzymes found in the liver, the small intestines, urinary bladder, lungs and skin. They mediate Phase II metabolism of xenobiotics containing an aromatic amine or a hydrazine group. They are genetically polymorphic with several important SNP's. Their substrates inclu...

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Main Author:	Yusuf, Wan Nazirah Wan
Format:	Thesis
Language:	English
Published:	2006
Subjects:	R5-920 Medicine (General)
Online Access:	http://eprints.usm.my/56195/1/00001660559%20DR%20W.N.W.Y.pdf
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id	my-usm-ep.56195
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spelling	my-usm-ep.561952023-01-03T02:12:49Z An Investigation Of The Genetic Polymorphisms Of N-Acetyltransferase 2 In Healthy Malays, Chinese And Indians In Malaysia And In Tuberculosis Patients On Isoniazid 2006-08 Yusuf, Wan Nazirah Wan R5-920 Medicine (General) N-acetyltransferases are enzymes found in the liver, the small intestines, urinary bladder, lungs and skin. They mediate Phase II metabolism of xenobiotics containing an aromatic amine or a hydrazine group. They are genetically polymorphic with several important SNP's. Their substrates include INH, pro-carcinogens and carcinogens. They therefore have importance in the pathogenesis of some cancers and in the pharmacotherapy of some diseases, notably tuberculosis. The objective of our study is to investigate the types and frequencies of NAT2 polymorphisms in the three major ethnic groups in Malaysia and among TB patients to forecast their influence on the rate of metabolism of INH. Malay, Chinese and Indian healthy volunteers were recruited from blood donation drives and their blood was taken for NAT2 genotyping. Newly diagnosed TB patients were also recruited. Blood for genotyping and phenotyping were collected at 4 hours after INH ingestion in patients who were treated with INH. Genotyping was done using nested allele specific multiplex peR methods and phenotyping by measuring plasma INH and Act-INH on the HPLC. Among healthy volunteers, the frequencies for NAT24, NAT25, NAT26, NAT27 and NAT212 in the 212 Malays, 172 Chinese and 175 Indians were 43.4%, 10.6%,25.5%,16.3% and 4.3% respectively among Malays; 64.0%, 3.2%,16.3%,12.2% and 0.3% among Chinese; and 22.6%,30.6%,30.9%, 6.9% and 3.4% among Indians. The types and frequencies for NAT2 alleles in TB patients were NAT24, NAT25, NAT26, NAT27 and NAT212 at 47.4%, 14.0%,21.2%, 12.9% and 2.3% respectively. The most common genotypes were NAT24/4, NAT2417, NAT24/5 and NAT26/6 with the frequencies of 25%, 18.9%, 15.2% and 15.2% respectively. There was no significant difference in allele frequencies of TB patients and healthy volunteers. For the 62 patients phenotyped, INH concentrations ranged from 0.31 to 4.17 j.Jg/ml and for Act-INH concentration from 0.01 to 2.48 j.Jg/ml. There was a trend for the metabolic ratios to increase with genotypes that predicted poorer activity. Correlation of genotype to MR was however imperfect. 2006-08 Thesis http://eprints.usm.my/56195/ http://eprints.usm.my/56195/1/00001660559%20DR%20W.N.W.Y.pdf application/pdf en public masters Perpustakaan Hamzah Sendut Pusat Pengajian Sains Perubatan
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	R5-920 Medicine (General)
spellingShingle	R5-920 Medicine (General) Yusuf, Wan Nazirah Wan An Investigation Of The Genetic Polymorphisms Of N-Acetyltransferase 2 In Healthy Malays, Chinese And Indians In Malaysia And In Tuberculosis Patients On Isoniazid
description	N-acetyltransferases are enzymes found in the liver, the small intestines, urinary bladder, lungs and skin. They mediate Phase II metabolism of xenobiotics containing an aromatic amine or a hydrazine group. They are genetically polymorphic with several important SNP's. Their substrates include INH, pro-carcinogens and carcinogens. They therefore have importance in the pathogenesis of some cancers and in the pharmacotherapy of some diseases, notably tuberculosis. The objective of our study is to investigate the types and frequencies of NAT2 polymorphisms in the three major ethnic groups in Malaysia and among TB patients to forecast their influence on the rate of metabolism of INH. Malay, Chinese and Indian healthy volunteers were recruited from blood donation drives and their blood was taken for NAT2 genotyping. Newly diagnosed TB patients were also recruited. Blood for genotyping and phenotyping were collected at 4 hours after INH ingestion in patients who were treated with INH. Genotyping was done using nested allele specific multiplex peR methods and phenotyping by measuring plasma INH and Act-INH on the HPLC. Among healthy volunteers, the frequencies for NAT24, NAT25, NAT26, NAT27 and NAT212 in the 212 Malays, 172 Chinese and 175 Indians were 43.4%, 10.6%,25.5%,16.3% and 4.3% respectively among Malays; 64.0%, 3.2%,16.3%,12.2% and 0.3% among Chinese; and 22.6%,30.6%,30.9%, 6.9% and 3.4% among Indians. The types and frequencies for NAT2 alleles in TB patients were NAT24, NAT25, NAT26, NAT27 and NAT212 at 47.4%, 14.0%,21.2%, 12.9% and 2.3% respectively. The most common genotypes were NAT24/4, NAT2417, NAT24/5 and NAT26/6 with the frequencies of 25%, 18.9%, 15.2% and 15.2% respectively. There was no significant difference in allele frequencies of TB patients and healthy volunteers. For the 62 patients phenotyped, INH concentrations ranged from 0.31 to 4.17 j.Jg/ml and for Act-INH concentration from 0.01 to 2.48 j.Jg/ml. There was a trend for the metabolic ratios to increase with genotypes that predicted poorer activity. Correlation of genotype to MR was however imperfect.
format	Thesis
qualification_level	Master's degree
author	Yusuf, Wan Nazirah Wan
author_facet	Yusuf, Wan Nazirah Wan
author_sort	Yusuf, Wan Nazirah Wan
title	An Investigation Of The Genetic Polymorphisms Of N-Acetyltransferase 2 In Healthy Malays, Chinese And Indians In Malaysia And In Tuberculosis Patients On Isoniazid
title_short	An Investigation Of The Genetic Polymorphisms Of N-Acetyltransferase 2 In Healthy Malays, Chinese And Indians In Malaysia And In Tuberculosis Patients On Isoniazid
title_full	An Investigation Of The Genetic Polymorphisms Of N-Acetyltransferase 2 In Healthy Malays, Chinese And Indians In Malaysia And In Tuberculosis Patients On Isoniazid
title_fullStr	An Investigation Of The Genetic Polymorphisms Of N-Acetyltransferase 2 In Healthy Malays, Chinese And Indians In Malaysia And In Tuberculosis Patients On Isoniazid
title_full_unstemmed	An Investigation Of The Genetic Polymorphisms Of N-Acetyltransferase 2 In Healthy Malays, Chinese And Indians In Malaysia And In Tuberculosis Patients On Isoniazid
title_sort	investigation of the genetic polymorphisms of n-acetyltransferase 2 in healthy malays, chinese and indians in malaysia and in tuberculosis patients on isoniazid
granting_institution	Perpustakaan Hamzah Sendut
granting_department	Pusat Pengajian Sains Perubatan
publishDate	2006
url	http://eprints.usm.my/56195/1/00001660559%20DR%20W.N.W.Y.pdf
_version_	1776101148478930944

An Investigation Of The Genetic Polymorphisms Of N-Acetyltransferase 2 In Healthy Malays, Chinese And Indians In Malaysia And In Tuberculosis Patients On Isoniazid

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