The Influence of Polymorphisms of Interleukin-17F Genes On the Susceptibility and Clinical Outcome of Multiple Myeloma.

Recent several cytokine studies have shown dysfunctional T cell responses in multiple myeloma (MM) patients. Regulatory T (Treg) cells, is essential for dominant immunologic tolerance. This decreased number and function of Treg cells in MM has been reported, leading to dysfunctional T cell responses. Interleukin-17 F(IL-17F) is a relatively new cytokine that regulates the adaptive and innate immune systems. In vivo studies in murine disease indicate that the Th17 lineage plays a pathogenic role in autoimmune disease. IL-17 polymorphism has been implicated in autoimmunity, including ulcerative colitis and asthma. Polymorphisms were studied, including the coding-region sequence variant single nucleotide polymorphism rs763780 (7488T/C), which causes a His-to-Arg substitution at amino acid 161 (H161R). We examined the single nucleotide polymorphisms (SNPs) in the promoter regions of the IL-17 genes in patients with MM, and analyzed the relationship between IL-17 SNPs and clinical features.

Eighty one patients with MM [age range, 40-83 years; stage I (n=9), stage II (n=21), stage III (n=51); IgA(n=13), IgG(n=48), IgD(n=1), non-secretary (n=3), Bence Jones(n=16)] and 100 healthy controls were included. Genomic DNA was isolated from peripheral blood using the DNA Kit (QIAGEN, Hilden, Germany). Genotyping in IL-17F was determined by PCR based technique. Genotype and allele frequencies were compared between the study groups using χ²-test. The characteristics and laboratory features of the MM patients with each IL-10 promoter polymorphism were compared using χ²-tests and student t-tests. Probability values <0.05 were considered statistically significant.

The frequencies of the genotypes in MM patinets were as follows: TT (76%), TC (18%), and CC (6%). Patients with MM had a higher frequency of The IL-17F CC genotype compared with healthy controls (P<0.05). No significant difference in the clinical presentation at diagnosis was indicated according to IL-17 polymorphism considering sex, Ig type, Durie-Salmon staging system, and international staging system.

Homozygosity of the H161R variant was associated with susceptibility of MM. These observations suggest that IL-17 may affect dysfunctional T cell responses in MM.

No relevant conflicts of interest to declare.