A Study Of The Association Between Polymorphisms Of The Tumor Necrosis Factor-a Promoter And Outcome After Thalidomide Therapy In Multiple Myeloma

TNF-a plays a key pathogenic role in the onset and development of MM (multiple myeloma). TNF-a expression is regulated at the transcriptional level and TNF-a expression associates with polymorphisms of the TNF-a gene promoter. Thal(thalidomide) inhibits TNF-a levels. It is necessary to study a relation between polymorphisms of TNF-a gene promoter regions and Thal therapy response in MM. The polymorphisms of the TNF-a gene promoter were studied using SSP-PCR (sequence-specific polymerase chain reaction assay), in the same time, Serum level of TNF-α was measured by ELISA. In our study, we don't find significant association of polymorphisms in -238 site of TNF-α gene promoter regions and susceptibility of MM between healthy control group and MM group, but, allele A frequency in -308 site of TNF-α gene promoter regions in MM patiens is significantly lower than that of healthy control group, speculating -308 A allele of TNF-α gene promoter is a protective factor. TNF-a levels have been found higher than that of control group. There is no association between polymorphisms in -238 -308 sites of TNF-α gene promoter regions and gene expression of TNF-α and response to Thal treatment.In the non-responding group , no significant changes in TNF-α level were observed after Thal therapy.In responding patients, serum levels of TNF-α were significantly lower, demonstrating that the role of TNF-a on the development of MM and TNF-a is a better marker of response to treatment.