Drug/xenobiotic metabolizing enzyme polymorphisms in a Turkish population

Kunak, Semih C.; Ada, Ahmet Oğuz; Karacaoğlan, Volkan; Soydas, Emre; Bilgen, Serdar; İşcan, Mümtaz

doi:10.5897/ajpp12.339

Afr. J. Pharm. Pharmacol.

2012

DOI: 10.5897/ajpp12.339

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Drug/xenobiotic metabolizing enzyme polymorphisms in a Turkish population

Semih C. Kunak¹,

Ahmet Oğuz Ada

Volkan Karacaoğlan³

et al.

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“…In the single study of GSTO1 A140D that included the Turkish population, Takeshita et al (17) observed that its distribution differed from Caucasian populations, and was more similar to African, Eastern Asian, and Brazilian populations. However, this finding is challenged by a great variety in the distribution of the same gene polymorphism even within one population (19)(20)(21)(22).…”

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confidence: 96%

Association Between Glutathione S-Transferase Omega 1 A140D Polymorphism in the Turkish Population and Susceptibility to Non-Small Cell Lung Cancer

Ada

Kunak

et al. 2013

Archives of Industrial Hygiene and Toxicology

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Recent years have seen a growing evidence of ethnic differences in the frequency of glutathione S-transferase omega 1 (GSTO1) A140D gene polymorphism, which is associated with various cancers such as breast and liver. Until now however, no association has been investigated between the GSTO1 A140D polymorphism and lung cancer. The aim of our study was to see if there was one in the Turkish population. To do that, we identifi ed GSTO1 A140D polymorphism in 214 unrelated healthy individuals and 172 patients with non-small cell lung cancer (NSCLC) using the polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of A/A (wild type), A/D (heterozygous mutant), and D/D (homozygous mutant) GSTO1 A140D genotypes in healthy subjects were 48 %, 41 %, and 11 %, respectively. In NSCLC patients they were 48 %, 45 %, and 7 %, respectively. We found no signifi cant association between the GSTO1 A140D gene polymorphism and NSCLC or its histological subtypes, namely squamous cell carcinoma or adenocarcinoma. Furthermore, this polymorphism did not correlate with smoking. Our study is the fi rst to show that the frequency of GSTO1 A140D gene polymorphism in the Turkish population is similar to other Caucasian populations and that this polymorphism is not associated with susceptibility to NSCLC.

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confidence: 96%

Association Between Glutathione S-Transferase Omega 1 A140D Polymorphism in the Turkish Population and Susceptibility to Non-Small Cell Lung Cancer

Ada

Kunak

et al. 2013

Archives of Industrial Hygiene and Toxicology

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Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1variants in Moroccan population

et al. 2014

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BackgroundSeveral pathogenesis and genetic factors influence predisposition to antituberculosis drug-induced hepatotoxicity (ATDH) especially for isoniazid (INH). However, the major susceptibility genes for ATDH are N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1). NAT2 gene determines the individual’s acetylator status (fast, intermediate or slow) to metabolize drugs and xenobiotics, while CYP2E1 c1/c1 genotype carriers had an increased risk of ATDH.Polymorphisms of the NAT2 and CYP2E1 genes vary remarkably among the populations of different ethnic origins.The aim of this study was to determine, for the first time, the frequency of slow acetylators in Moroccan population by genotyping of NAT2 gene variants and determining the genotype c1/c1 for CYP2E1 gene, in order to predict adverse effects of Tuberculosis treatment, particularly hepatotoxicity.ResultsThe frequencies of specific NAT2 alleles were 53%, 25%, 2% and 4% for NAT2*5, NAT2*6, NAT2*7 and NAT2*14 respectively among 163 Moroccan studied group. Genotyping of CYP2E1 gene, by real-time polymerase chain reaction using TaqMan probes, revealed frequencies of 98.5% for c1/c1 and 1.5% for c1/c2 among 130 Moroccan studied group.ConclusionThe most prevalent genotypes of NAT2 gene in Moroccans are those which encode slow acetylation phenotype (72.39%), leading to a high risk of ATDH. Most Moroccans are homozygous for c1 allele of CYP2E1 gene which aggravates hepatotoxicity in slow acetylators.This genetic background should be taken into account in determining the minimum dose of INH needed to treat Moroccan TB patients, in order to decrease adverse effects.

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Drug/xenobiotic metabolizing enzyme polymorphisms in a Turkish population

Cited by 2 publications

References 46 publications

Association Between Glutathione S-Transferase Omega 1 A140D Polymorphism in the Turkish Population and Susceptibility to Non-Small Cell Lung Cancer

Association Between Glutathione S-Transferase Omega 1 A140D Polymorphism in the Turkish Population and Susceptibility to Non-Small Cell Lung Cancer

Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1variants in Moroccan population

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