engleski

Study of SNP polymorphisms in promotor region of TNF-alpha in Croatian population

The immune system is a complex network of cells that are involved in the protection of humans against infectious agents and tumor growth. Inherited polymorphisms in immuno-modulatory genes may contribute to variation in immune function and genetic susceptibility for complex disease, including cancer. TNF is a cytokine produced by activated monocytes and macrophages, which play a key role in the inflammatory response. Increased serum TNF  levels have been described in cancer patients, and are associated with an adverse disease outcome. TNF gene is mapped to chromosome 6p21.3 in the region of the major histocompatibility gene complex, and a large number of polymorphisms of its promoter, called "high-production" polymorphisms, have been described. Some authors have reported the association between these polymorphisms and susceptibility to develop Crohn's disease. Increased amounts of TNF play an essential role in the pathogenesis of this disease and anti-TNF therapies have shown substantial effects on lowering its activity. The aim of our study was to estimate allelic frequency for two promotor region SNPs in TNF gene, one at position -238 and the other at position -308, in the Croatian population. DNA was obtained from peripheral blood of patients with colon cancer and healthy unrelated volunteers. We used PCR and RFLP methods for polymorphisms analysis. The frequency of heterozygous with alleles associated with elevated TNF production was: 6 % for allele variant G-238*A and 20 % for allele variant G-308*A. Twenty-five percent of the samples from Croatian population were heterozygous for one or both of these “ high-production” polymorphisms in the TNF gene. Allele variant G-238*A was more common in the population with colon cancer in the comparison to healthy volunteers. The association between these polymorphisms and colon cancer has to be investigated in the future studies.

TNF-alpha; SNP; Croatian population

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