TNF-α and MDM2 Polymorphism in Pathogenesis of Chronic Lymphocytic Leukemia.

Apoptosis dysfunction one of the main process in pathogenesis of CLL. One of the apoptosis regulators is cytokine TNF- α. In normal condition in cells expressed protein p53 and main tumor suppressor MDM2. The high expression of protein MDM2 is oncogenic factor. The gene of protein MDM2 placed on the long arm 12 chromosome (12q14.3-12q15). Our aim was studying of frequencies of polymorphic variants of genes TNA-α and MDM2.

We observed 133 patients with CLL (male-75, female-58). The median age was 49. The control group was 196 healthy donors from the same region, same ethnic group, age 47 (male-107, female-89).

In patient group in polymorphic locus -308G>A gene TNFα genotype GG met often than in control group (82% and 65% accordingly, χ2=10,674; p=0,002). On the contrary genotype GA authentically often met in group of healthy individuals (33 %) whereas its frequency in group of CLL patients was 17 % (χ2=8,837; p=0,004). Frequency of allele G a polymorphic locus-308G> A gene TNF-α in group of CLL patients it is authentic more than in control group (91 % and 81 % accordingly, χ2=10,411; p=0,002). Distinctions also were observed on frequencies of allele A, in control group 19 % and 9 % and in the group of CLL patients (χ2=10,411; p=0,002). On frequencies of genotype AA of authentic distinctions it is not revealed. Thus, as a result of research it has been shown that markers of risk of CLL development are genotype GG (OR=2,468; 95 % CI 1,452-4,194) and allele G (OR=2,244; 95 % CI 1,384-3,638) of polymorphic locus-308G> A gene TNF-α. Opposite stability markers are genotype GA (OR=0,432; 95 % CI 0,252-0,741) and allele A (OR=0,446; 95 % CI 0,275-0,724). The analysis of distribution of frequencies of a polymorphic locus 309T> G gene MDM2 in patients group and group of healthy individuals has shown statistically authentic distinctions, on allele T, frequency in group of CLL patients was 54 % and in group of healthy individuals was 63 % (χ2=4,141; p=0,042; OR=0,679; 95 % CI 0,475-0,972). Also in allele G 46 % in patient group against control group - 37 % (χ2=4,141; p=0,042; OR=1,474; 95 % CI 1,03-2,108).

Thus, the cited data of researches testifies to the important role of genes TNF α, MDM2 in CLL development. In particular genotypes GG and allele G in a polymorphic locus-308G> A gene TNF-α and allele G in a polymorphic locus 309T> G gene MDM2 have appeared as markers of the raised risk in CLL development. On the contrary genotype GA and allele A in a polymorphic locus-308G> A gene TNF α and allele T in a polymorphic locus 309T> G gene MDM2 are the markers of the raised stability to CLL development.

No relevant conflicts of interest to declare.