title: The frequency and distribution of thiopurine S-methyltransferase alleles in south Iranian population.
abstract: Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathiopurine. Variability in TPMT activity is mainly due to genetic polymorphism. The frequency of the four allelic variants of the TPMT gene, TPMT*2 (G238C), TPMT*3A (G460A and A719G), TPMT*3B (G460A) and TPMT*3C (A719G) were determined in an Iranian population from south of Iran (n = 500), using polymerase chain reaction (PCR)-RFLP and allele-specific PCR-based assays. Four hundred seventy four persons (94.8%) were homozygous for the wild type allele (TPMT*1/*1) and twenty five people were TPMT*1/*3C (5%). One patient was found to be heterozygous in terms TPMT*1 and *2 alleles with genotype of TPMT*1/*2 (0.2%). None of the participants had both defective alleles. The TPMT*3C and *2 were the only variant alleles observed in this population. The total frequency of variant alleles was 2.6% and the wild type allele frequency was 97.4%. The TPMT*3B and *3A alleles were not detected. Distributions of TPMT genotype and allele frequency in Iranian populations are different from the genetic profile found among Caucasian or Asian populations. Our findings also revealed inter-ethnic differences in TPMT frequencies between different parts of Iran. This view may help clinicians to choose an appropriate strategy for thiopurine drugs and reduce adverse drug reactions such as bone marrow suppression.
authors.affiliation: Department of Internal Medicine, Gastroenterology and Hepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Moini
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Ghaderi
authors.forename: Mohamad Mehdi
authors.initials: MM
authors.lastname: Sagheb
authors.forename: Ali Reza
authors.initials: AR
authors.lastname: Tavasolli
authors.forename: Negar
authors.initials: N
authors.lastname: Azarpira
authors.forename: Masumeh
authors.initials: M
authors.lastname: Darai
authors.forename: Bita
authors.initials: B
authors.lastname: Geramizadeh
mesh_terms: D000483:Alleles; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics*; D005828:Genetics, Population; D005838:Genotype; D005843:Geography; D006801:Humans; D007492:Iran; D008780:Methyltransferases / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase