Interleukin-6 gene-174 G/C promoter polymorphism and its association with clinical profile of patients with multiple myeloma

Aim In multiple myeloma (MM), the growth and survival of myeloma cells is controlled by interleukin-6 (IL-6), the plasma levels of which is controlled by a guanine/cytosine substitution occurring in position -174 of IL-6 gene promoter region. We studied the occurrence of IL-6-174 G/C polymorphism in patients of MM and correlated the presence of genotypes with serum IL-6 levels and tumor staging. Methods One hundred three patients with MM and 117 age- and sex-matched healthy controls were staged by International Staging System. IL-6 genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis. Serum levels of IL-6 were assessed by enzyme-linked immunosorbent assay. Results Frequency of GG, GC and CC genotypes did not differ significantly between cases (GG 52%, GC 40%, CC 9%) and controls. The median serum level of IL-6 was significantly higher among the GC genotype versus other genotypes (24 ng/mL, P = 0.007) as compared with the GG versus other genotypes (12 ng/mL, P = 0.001). GC was associated more with stage 3 disease (27%) than was GG (11%) or CC (22% P = 0.001). Conclusions At position 174 of the IL-6 promoter, patients with GC genotype had higher serum levels of IL-6 and presented with more severe disease compared with patients with GG or CC genotype.