P-210: Evaluation of IL-6, IL-1β and TNF-α polymorphisms in Multiple Myeloma patients

Introduction: Multiple Myeloma (MM) is a hematological neoplasm characterized by clonal proliferation of plasma cells, resulting from the action of inflammatory cytokines, angiogenic and vasculogenic factors. Genetic alterations related to such factors have been studied in order to understand how these changes modify the onset and evolution of the disease. Aims- To study the polymorphisms in the IL-1β , IL-6 and TNF-α genes and their potential impact on MM biochemical changes


Methods: A cross-sectional study was carried out involving 20 patients transplant eligible newly diagnosed MM from the MAXDARA trial a phase 2 study and 55 healthy controls. The genotyping was performed with polymerase chain reaction (PCR) and DNA sequencing by B3500xL Genetic Analyzer for Human Identification (Apllied Biosystems,Massachusetts, EUA). The sequencing results were analyzed by BioEdit (Sequence-Alignment-Editor-7.2.5) and compared with NCBI databases using BLAST.


Results: Seventy-five % (n=17) of these MM patients were black or mixed race, 63.64% (n=14) were female and 28.5% (n=6) and 33.3% (n=7) were diagnosed with R-ISS- II and III, respectively. Polymorphism analysis in the IL-6 gene -174G/C rs1800795 showed a frequency of 52.38% (n=11) for the homozygous wild type (GG) genotype, 28.57% (n=6) for the heterozygous genotype (GC) and 19.05% (n=4) for the homozygous variant genotype (CC) in the MM group and 79.25% (n=42), 19.87% (n=10) and 1.89% (n=1) for the GG, GC and CC genotypes, respectively in the control group. The analysis with a dominant model demonstrated an odds ratio (OR) of 3.47 (1.17 – 10.25 CI: 95.0%), p-value = 0.042, and the allele frequencies showed an OR of 3.91 (1.62 – 9.43 CI: 95.0%), p-value=0.003. The association of polymorphisms with biochemical markers showed that MM individuals with GA/AA genotypes for the TNF-α rs673 polymorphism had higher levels of calcium than individuals with the GG genotype (p=0.006). For the TNF-α rs1800629 polymorphism, individuals with the GG genotype had higher levels of total protein than GA/AA individuals (p =0.03).


Conclusions: The present study suggests that the presence of the IL-6 -174 G/C rs1800795 polymorphism appears to be associated with MM. New studies with more MM patients involving polymorphisms in the IL-6 and TNF-α genes are necessary to confirm these results.