Analysis of polymorphism at site -174 G/C of interleukin-6 promoter region in multiple myeloma

Abstract

It is well established that interleukin-6 (IL-6) is an essential growth factor for multiple myeloma (MM) and patients with increased IL-6 levels have a poor prognosis. In healthy subjects, the presence of the C allele at a polymorphic site (-174 G/C) of the IL-6 gene is related to low IL-6 levels. In view of the potential association of this particular polymorphism with IL-6 concentration, and the relevance of IL-6 in MM pathogenesis, the objective of the present study was to investigate the prevalence of IL-6 (-174 G/C) promoter polymorphism and its association with development of MM in Brazilian individuals. We investigated the prevalence of these alleles in 52 patients and 60 healthy subjects (matched by age, sex, and race) of a Brazilian population. Thirty patients were male (42.4%), 24 (46.2%) were white and the median age at diagnosis was 58.5 years (range: 28 to 84 years). To determine the IL-6 (-174 G/C) polymorphism, molecular analysis was performed by polymerase chain reaction followed by endonuclease restriction digestion. The genotype distributions observed in the group of patients were 4% CC, 42% GC and 54% GG. The C allele frequency was 0.25. These results were similar to the control group, suggesting no impact of this polymorphism on the susceptibility to MM.

Prognostic Importance of Single-Nucleotide Polymorphisms in IL-6, IL-10, TGF-β1, IFN-γ, and TNF-α Genes in Chronic Phase Chronic Myeloid Leukemia

“…IL-6 is associated with poor prognosis in various malignancies (Deans et al, 2007;DeMichele et al, 2009). Nevertheless, it was reported that this cytokine was not associated with multiple myeloma or primary cutaneous melanoma (Martinez-Escribano et al, 2003;Duch et al, 2007). No data are available on a possible association with CML.…”

Cytokine Gene Polymorphisms in Colorectal Cancer

“…A possible cause for the conflicts and mismatches, like those observed here and the earlier study in allele and genotype distributions, may be the differences in racial or ethnical backgrounds. Duch et al analyzed 52 patients with multiple myeloma and found that the G allele frequency was higher in the Brazilian population than in the European population (Duch C et al, 2007). Nowadays Yeh et al observations on the allele and genotype distribution of the IL-6 −174 G/C polymorphism demonstrated that there are low frequencies of the G allele and GG genotype in the Taiwanese CRC population compared to the Western counterpart (Yeh et al, 2009).…”

Genetics and molecular epidemiology of multiple myeloma: The rationale for the IMMEnSE consortium (Review)

“…In general, cytokine-encoding genes have been extensively investigated (70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86), due to the high degree of polymorphisms characterized in these genes and to their important role in the bone marrow microenvironment and B-cell development.…”

“…Several reports investigated SNPs in IL6, IL6R and IL6ST genes (75,76,(80)(81)(82) and up to date, several studies failed to evidence association with the well studied IL6 promoter -174G/C SNP (rs1800795) (70,75,(80)(81)(82). In one study the IL6 -572G/C (rs1800796) was associated with an increased risk to develop MM for carriers of the -572C allele (75).…”