Background: Patients with low or intermediate TPMT enzyme activity are at increased risk to develop severe hematopoietic toxicity after taking standard doses of thiopuring medications. The aim of this study was to determine the frequency of four allelic variants of the TPMT gene in an Iranian population. Methods: In this cross sectional study, samples were obtained from 127 Iranian volunteers in Shariati hospital and were analyzed using PCR-RFLP and Allele Specific PCR techniques to determine the presence of common TPMT Polymorphisms in this population. Results: Mutant TPMT alleles were found in 11.8% of subjects (15 out of 127). Nine had TPMT*2, 4 TPMT *3C and 2 TPMT*3A. Conclusions: Our data showed the necessity of TPMT polymorphisms assessment before administration of thiopurine drugs.

Objective: Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. Low activity phenotypes are correlated with several mutations in the TPMT gene and adverse drug reactions. The molecular basis for dissimilar enzymatic activity of TPMT has been established in Caucasians, African-Americans and Southwest Asians, but it remains to be elucidated in Iranian population. Until present, no study on Iranian population has been performed on the known alleles of TPMT. The aim of this study was to investigate the frequencies of four of the most common variants of this gene.Materials and Methods: This study was conducted during 2007 at the Department of Hematology, Tarbiat Modares University, Tehran, Iran. Using PCR-RFLP and allele specific PCR techniques, allelic variants of the TPMT gene TPMT*2 (G238C), TPMT*3B (G460A), TPMT*3C (A719G) and TPMT*3A (G460A and A719G) were genotyped in a normal population of 127 Iranians.Results: In this study TPMT*2 showed a prevalence of 7.08%. TPMT*3C and *3A were found in 2.47% and 2.18% of the samples, respectively. TPMT*3B variant was not detected in Iranian subjects. 112 out of 127 participants showed homozygote wild type allele.Conclusion: This study is the first to analyze TPMT allele frequencies in a sample of Iranian population and indicates that TPMT*2 is the most common allele (7.08%) in this population. These results can help to organize national pretreatment strategies in patients with acute lympho blastic leukemia (ALL) or other diseases requiring thiopurine medication in their standard therapy.

Pneumoviruses are responsible for significant respiratory disease in their hosts and represent a major problem for human and animal health. Pneumoviruses are members of the family Paramyxoviridae, subfamily Pneumovirinae and the virus particles consist of a negative-sense, nonsegmented RNA genome within a helical nucleocapsid structure enveloped in a lipid membrane derived from the host cell. Over the past four decades much work has extended our understanding of the molecular biology and pathogenesis of pneumoviruses but despite this only limited treatments and prophylaxis are available. The human pathogen, respiratory syncytial virus (hRSV) which belongs to the genus of Pneumovirus is the best characterized of the subfamily. HRSV is the major cause of hospitalisation of very young children with respiratory disease worldwide. No vaccine is available though new treatments offer some respite for children in the highest risk groups, the immunocompromised and children with congenital heart disease. The recently discovered human pathogen human metapneumovirus (hMPV) belongs to the genus Metapneumovirus and recent data indicates that this virus is second only to hRSV in terms of disease impact. The pneumoviruses also include agents of veterinary importance such as bovine respiratory syncytial virus (bRSV), ovine and caprine RSV, and pneumonia virus of mice (PVM: all in the genus Pneumovirus) and avian metapneumovirus (APV: genus Metapneumovirus). The development of reverse GENETICS systems for negative strand RNA viruses has opened the possibility of manipulating the virus genomes to identify genes involved in pathogenesis and to explore the biological consequences of specific mutations. This information is informing the rational design of new vaccines. These plasmid-based systems have shown that for all paramyxoviruses the N, P and L proteins are necessary and sufficient for RNA replication. However, the pneumoviruses differ from the other family members in that fully efficient transcription from the virus genome requires the presence of an additional protein encoded by the M2 gene. The present article reviews pneumovirus biology and molecular GENETICS including a discussion of current concepts of Pneumovirus reverse GENETICS.