Voltage-gated sodium channels are critical for the generation and conduction of nerve impulses. These channels are responsible for transmitting noxious information to the central nervous system. Individual isoforms of voltage-gated sodium channels have been linked to particular type of pain. Four isoforms of Na⁺ channels, Na⁺ 1.3, 1.7, 1.8, and 1.9, have been implicated in the pathogenesis of neuropathic pain. New genetic data from both human studies and transgenic mouse models suggest that specific voltage-gated sodium channel subtypes are associated with specific types of pain and, as consequence, may be useful analgetic drug targets for a variety of pain types including neuropathic pain.

A polymorphic polythymidine (Tn) locus located within splice site of IVS8 of the cystic ?brosis transmembrane conductance regulator ( CFTR ) gene is associated with variable efficiency of exon 9 splicing. Genes that carry 5T allele have the highest levels of exon 9 skipping. (TG)m tract located immediately upstream of the Tn can also modulate exon 9 skipping and may account for the partial penetrance of the 5T allele. Analysis of (TG)_mTn polymorphism is important for the diagnosis of congenital bilateral absence of the vas deferens (CBAVD) and for investigation of polymorphic backgrounds of the CFTR gene. To detect poly-T-alleles, TG -repeats and molecular haplotyping (TG)_mTn we developed nested PCR and fragment analysis. Allele frequencies of the 5T , 7T and 9T (N=2261) were consistent with the distribution for Caucasians. TG -repeats and (TG)_mTn haplotypes were analyzed for 292 individuals. The major allele was 11TG (59.0%) аnd the major haplotypes - 7T-11TG (52.3%). 9T allele was mainly linked with 10TG (71.9%). 5T-12TG and 5T-13TG haplotypes were found in 18.0% and 1.1% of 5T chromosomes.

In the context of studying a genetic causes of extremely rare coexistence of atopic bronchial asthma (BA) and tuberculosis (TB) we’ve held an associative analysis of polymorphism IL1B, IL8, IL10, TNF, TNFRSF1B, CXCL10 genes in 713 individuals living on the Tomsk and Tomsk region. The relation of rs56061981* CXCL10 in the development of TB was established. Furthermore, association of variant rs1800872 of IL10 with the development of BA and pulmonary TB either was ascertained. Thus, obtained data support the importance of IL10 gene in BA and TB development that require further research IL10 signaling pathway to clarify the possible role in pathogenesis of the «inverse» comorbidity between infectious and allergic diseases.

Our previous research establishes that changes of expression of the ATP-binding cassette genes family ( ABCB1 , ABCB3 , ABCC1 , ABCC2 , ABCC5 , ABCG1 , ABCG2 ) is connected with the neoadjuvant chemotherapy effect. However, the mechanism of regulation of resistance gene expression remains unclear. As many researchers believe, single nucleotide polymorphisms can be involved in this process. Materials and methods. Thereupon, microarray analysis is used to study polymorphisms in ATP-binding cassette genes. The study group 84 patients with breast cancer. The test material as tumor biopsy samples were used to treat and operation after chemotherapy. The evaluation of genes expression was performed by real time PCR. Results. Total 195 single nucleotide polymorphisms 7 gene family of ABC-transporters have been analyzed. It is thus found that MDR gene expression is connected with 8 polymorphisms, i.e. ABCB1 rs2235035 , ABCB3 rs241430 , ABCB3 rs241429 , ABCC1 rs17205838 , ABCC1 rs35596 , ABCC2 rs4919395 , ABCC2 rs2756103 and ABCG2 rs59409230 which participate in the regulation of expression of own genes. Conclusions. Therefore, this work shows that the majority of mutations and polymorphisms of ABC genes have a substantial impact on the ATP-binding cassette transporter regulation, it can give more information about the mechanisms of ABC regulation of gene expression and the formation of chemoresistance.

A short review represents comprehensive information in ABCC11 gene polymorphism including our own data about the distribution genotypes and alleles frequencies of ABCC11 (rs17822931) in some ethnic groups of Russia. The protein encoded by ABCC11 gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. Non-synonymous single nucleotide polymorphisms (SNP) 538G >A (rs17822931; Gly180Arg) in the ABCC11 gene determines the type of earwax in individuals has shed light on the novel function of this ABC transporter in apocrine glands. The wild-type (Gly180) of ABCC11 gene associated with wet-type earwax, axillary osmidrosis, and colostrums secretion from mammary gland as well as the potential risk of mastopathy. The SNP (538G>A) in the ABCC11 gene is suggested to be a clinical biomarker for the prediction of chemotherapeutic efficacy. The aim of this work is to study the genotypes and alleles distribution in the ethnical groups of Russia by molecular genetics methods. In the results data on the ABCC11 (rs17822931) polymorphism in three small ethnic group of Russia are represented in this study. The frequencies of ABCC11 (rs17822931) alleles (*G and *A) which determine wet and dry types of ear wax are equal were in khants population to 0,3291 and 0,6709; in nenets 0,3172 and 0,6828 (Western Siberia) and in kalmyks of the Lower Volga to 0,1620 and 0,8380 accordingly.

The aim of the study was to investigate clinical parameters and inflammatory markers in cystic fibrosis patients (CF) with TNF and LTA gene polymorphisms: a G-to-A transition in position -308 in the promoter region of the TNF gene ( rs1800629 , TNF-308 ) and a A-to-G transition at position +252 in the first intron of the LTA gene (rs909253, LTA+252 ). The study included 120 children and 80 adults with CF. All patients had regularly (every 3-6 months) attended the Russian Pediatric Clinical Hospital or Pulmonology Research Institute for routine antibiotic therapy and clinical examination. The patients with genotype LTA+252AA (low production of lymphotoxin-alpha, LTa) were significantly older than those with genotypes LTA+252GG/AG (high LTa production). In the same time the groups did not differ significantly in term their pulmonary function test results, frequency of diabetes development, or number of died patients. However, in group with genotypes LTA+252GG/AG 5 of 6 patients with diabetes were below 14 years old. In contrast, there was only patient below 14 among 10 patients with diabetes from group with genotype LTA+252AA (р = 0,007). Patients with LTA+252GG/AG genotypes had elevated plasma levels of IL-17A и IFNg. The same trend was found in relation to plasma IL-8 concentrations. In conclusion, the children with genotypes LTA+252GG/AG had more often need of hospitalization and demonstrated increased rate of diabetes development. These phenomena may be partly explained by increased grade of systemic inflammation in the carriers of LTA+252G alleles. Further investigations with prolonged observation period and increased number of participants are needed to assess the risks of early diabetes development in CF patients with LTA+252 polymorphisms.