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Many studies have been done to determine the distribution of acetylator phenotypes among populations of different geographic origin. The goal of this study was to investigate the acetylator phenotypes of the Iranian population and compare them between tubercular patients and healthy subjects. The study population consisted of two groups; the first group included 100 newly diagnosed tubercular patients and the second group consisted of 100 healthy subjects. Acetylator phenotype was determined from the metabolic ratio of acetyl-isoniazid to isoniazid in the plasma samples. Metabolic ratio was used to classify subjects as slow (≤0.70) or fast acetylators (>0.70). In the tubercular patients, the frequencies of slow and fast acetylator phenotypes were 62 and 38%, respectively. Of the healthy individuals, 45% were found to be slow acetylators and the remaining 55% were fast acetylators. It seems that tubercular patients metabolize isoniazid more slowly than healthy individuals. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of mutations at the polymorphic gene coding for arylamine N-acetyltransferase 2 (NAT2, EC 2.3.1.5) and NAT2 genotypes associated with slow acetylation in healthy Iranian individuals. Methods: The polymorphisms in the NA T2 gene from 88 unrelated healthy subjects (48 men/40 women) from the general Tehran population were discriminated using polymerase chain reaction (PCR) with allele-specific primers (341 C> T) and PCR-restriction fragment length polymorphism analysis (481 C > T, 590 G> A, and 857 G>A). Results: Frequencies of the studied polymorphisms showed the most common alleles to be NAT2*4 (0.43) and NAT2*5, 481 C>T (0.32), followed by NAT2*6 (0.19) and NAT2*7 (0.06), previously referred to as WT, M 1, M2, and M3, respectively. The most prevalent genotypes were NAT2*4/*5 [(31.8%; 95% confidence interval (CI): 29-34%] and *4/*4 (18.2%; 95% CI: 1621 %). When grouped according to the expected phenotypical effects, the resulting genotypes revealed the significant prevalence of the subjects with slow (32.9%) and intermediate (48.9%) acetylation status compared with wild-type rapid (18.2%) acetylators (P<0.01). Conclusions: The overall allele pattern and acetylator status distribution in Iranians displayed the considerable prevalence of "slow acetylators" over "rapid acetylators," similar to those of Caucasians except for a minor difference observed in the frequency of the NAT2*7 allele. Nucleic acid testing for common NA T2 mutations might be a potentially useful tool for an accurate phenotype interpretation and identification of Iranian individuals at risk. [ABSTRACT FROM AUTHOR]

1. Xenobiotic-metabolizing enzymes constitute an important line of defence against a variety of carcinogens. Many are polymorphic, constituting the basis for the wide interindividual variation in metabolic capacity and possibly a source of variation in the susceptibility to chemical-induced carcinogenesis. The aim of the present study was to determine the frequencies of important allelic variants in the N-acetyltransferase 2 (NAT2) and glutathione S-transferase (GST) genes in the Iranian population and compare them with frequencies in other ethnic populations. 2. Genotyping was performed in a total of 229 unrelated healthy subjects (119 men, 110 women) for NAT2 and 170 unrelated healthy subjects (89 men, 81 women) for GST from the general Tehran population. A combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was applied for typing of NAT2 polymorphisms. Detection of GSTM1 and GSTT1 null alleles was performed simultaneously using a multiplex PCR assay. 3. The frequencies of specific NAT2 alleles were 0.299, 0.314, 0.380, 0.007 and 0.000 for 4 (wild-type), 5 (C481T, M1), 6 (G590A, M2), 7 (G857A, M3) and 14 (G191A, M4), respectively. The most prevalent genotypes were NAT2 5/6 (29.70%) and 4/6 (21.40%). The GSTM1- and GSTT1-null alleles were detected in 44.7 and 21.2% of subjects, respectively. 4. We found that Iranians resemble Indians with regard to allelic frequencies of the tested variants of NAT2. The predominance of slow (49.36%) and intermediate (41.47%) acetylation status compared with wild-type rapid acetylation status (9.17%) in the study group suggests the significant prevalence of the slow acetylator (SA) phenotypes in the Iranian population. Our data confirmed that Iranians are similar to other Caucasian populations in the frequency of both GSTM1- and GSTT1-null alleles.

The acetylation polymorphism is one of the most common inherited variations in the biotransformation of drugs and chemicals. Its association with drug toxicity and increased risk of developing certain diseases and certain types of chemically induced cancers has made it one of the oldest and best studied examples of pharmacogenetic conditions. N-Acetylation of sulfamethazine was studied in 74 unrelated healthy Iranian volunteers. The frequency of slow acetylators, determined by using free and total plasma sulfamethazine concentrations, was 78.4%. The mean acetylation ratio was 19.48% for slow acetylators, and the frequency of the recessive allele controlling slow acetylation was found to be 0.88. This percentage is similar to that observed in various Arab countries and higher than that observed in Europeans.