Cytokine gene polymorphism in Iranian patients with chronic myelogenous leukaemia.

Chronic myelogenous leukaemia (CML) is a disorder of the haematopoietic stem cell that results in malignant expansion of myeloid cells with a cytogenetic abnormality, and translocation between chromosomes 9 and 22, known as the Philadelphia chromosome. It has been hypothesized that genetic factors other than histocompatibility disparity may play a role in predisposition to developing CML. In this regard, T helper types 1 and 2 (Th1 and Th2) cytokines and their gene polymorphism seem to be important. Overall expression and secretion of cytokines are dependent, at least in part, on genetic polymorphism (nucleotide variations) within the promoter region or other regulatory sequences of cytokine genes. The majority of polymorphisms described are single nucleotide polymorphism (SNPs). The objective of this study was to analyse the genetic profile of Th1 and Th2 cytokines in 30 Iranian patients with CML and 40 healthy subjects. In the patients and control subjects, the allelic and genotype frequencies were determined for the cytokine genes. All typing were performed with a polymerase chain reaction-sequence-specific primers (PCR-SSP) assay. Allele and genotype frequencies were calculated and compared with those of normal controls. The results showed that the most frequent genotypes in our patients were transforming growth factor (TGF)-beta TG/TG, interferon (IFN)-gamma AT, interleukin (IL)-4 CC at position -590, TT at position -33, and IL-10 ACC/ACC and ATA/ATA. In contrast, the genotypes TGF-beta CG/CG, IL-2 TT at position -330, IL-4 CT at position -590, CT at position -33, and IL-10 GCC/ACC were seen at much lower frequencies. The results suggest that production of TGF-beta in CML patients is higher and production of IL-4 and IL-10 is lower than in normal subjects.