Familial Mediterranean fever (FMF) is a monogenic inherited autoinflammatory disease characterized by recurrent episodes (attacks) of fever, serositis of different localization, arthritis, erysipelaslike rashes. Eastern Mediterranean persons (especially Turks, Armenians, Arabs, Sephardic Jews) are most frequently affected. Nowadays the disease is registered throughout the world because of migration processes. Potential complications of FMF (fibrosis and amyloidosis) and their treatment with colchicine may affect the reproductive system either by salpinx obstruction causing mechanical infertility, or by excessive formation of defective sperm and oocytes, either due to ovarian /testicular insufficiency. Amyloidosis can lead to female and male infertility with amyloid preponderance in the ovaries and testicles. Colchicine rarely induces oligo/ azoospermia in men. In women, disovulation and peritoneal adhesion were the main causes of infertility in the past. In recent years, the fertility situation has improved considerably due to the use of colchicine. The review summarizes current information on the relationship between female and male fertility with FMF and colchicine; modern approaches to restoring reproductive function in infertility are outlined. The focus is on the aspects of the safety of therapy, the main provisions of which are presented in the clinical recommendations for treatment of the FMF of the European Anti-Rheumatic League (EULAR, 2016).

Alpha-1 antitrypsin deficiency is a genetic disorder characterized by low level of alfa-1-antitripsin protein (A1AT) in the blood. Usually, A1AT deficiency results in chronic obstructive pulmonary disease (COPD), emphysemas, liver disease and vessels damaging. A1AT is the main inhibitor of serine proteases in human blood. A1AT deficiency is caused by mutations in the gene SERPINA1. The most common SERPINA1 allelic variants are S (p.Glu288Val) and Z (p.Glu366Lys). However, the most of documented severe cases of A1AD are associated with PIZZ genotype. PIZZ genotype patients have loss-of-function phenotype due to accelerated lung parenchyma destruction resulting in emphysema. Z mutation genotype leads to blocking of 85% synthesized protein in hepatocytes due to wrong folding and polymerization. Accumulation of the bodied protein in hepatocytes endoplasmic reticulum results in chronic liver disease, cirrhosis and other liver pathologies. A1AT deficiency is a common disorder, however, this diagnosis is established in a small part of the patients. A1AT deficiency is often misdiagnosed as COPD, asthma or сryptogenic liver disease. Usually, due to underestimating the prevalence of the disease and its unspecific symptoms, the diagnosis delay is more than 5 years (on average about 8 years). Nowadays it is possible to treat lung form of A1AT deficiency used the augmentation therapy, that bases on intravenous infusions of pure human A1AT. Also, the active development of new drugs to improve the prognosis in the patients with liver pathology is ongoing. Modern approaches of A1AT deficiency treatment, focused on gene therapy, are becoming a promising direction in the managing of both pulmonary and hepatic pathology with A1AT deficiency.

Obesity is a critical risk factor for type 2 diabetes mellitus (T2D). Hepatic nuclear factor 1 β (HNF1B) controls the glucostatic function of pancreatic islets of Langerhans and is associated with the development of T2D in the European and Asian populations. However, studies evaluating the contribution of genetic variants at HNF1B to the pathogenesis of the disease in Russian population have not been conducted to date. The aim of this work was to study the association of the polymorphic variant rs4430796 (A>G) in the intron of the HNF1B gene with parameters of glycemic profile and redox homeostasis, as well as the risk of developing T2D in citizens of Central Russia, taking into account their gender and body mass index. The study included 3206 participants, 1579 patients with T2D and 1627 healthy volunteers. Genotyping was performed using iPLEX technology on a genomic time-of-flight mass spectrometer MassArray 4 (Agena Bioscience). For the first time in the Russian population, the relationship of the rs4430796 polymorphism at the HNF1B gene with an increased risk of developing T2D (OR 1,24, 95CI 1,05-1,47, p=0,011) was established. A gender-stratified analysis found that the association is characteristic only for females with overweight (OR 1,54, 95CI 1,06-2,22, p=0,02) and obesity (OR 2.07, 95CI 1,14-3,77, p=0.047) and is absent in individuals with normal body weight, regardless from the gender. The studied SNP is associated with an increased content of hydrogen peroxide (p=0,012) and a lower level of total plasma glutathione (p=0,041) in females, whereas in diabetic males the G/G genotype is associated with a decrease in the concentration of C-peptide (p=0,004) and an increase in blood glucose concentration (p=0,015). Bioinformatic analysis confirmed the negative effect of the alternative G allele on the expression of the HNF1B gene, as well as its relationship with hypermethylation of the gene at different periods of life, which leads to low expression of HNF1B in carriers of variant rs4430796. Conclusions: It was found for the first time that the polymorphic variant rs4430796 of the HNF1B gene is associated with a predisposition to T2D, whereas its relationship with the disease is sex-specific and depends on body mass index.

Cerebral stroke (CS) is the leading factor in cognitive decline and dementia and ranks third in the structure of mortality worldwide. Oxidative stress is the basic mechanism of brain damage after cerebral ischemia-reperfusion. The thioredoxin system is the most important antioxidant barrier of the cell, capable of regulating its redox status. The aim of this study was to investigate the association of the common single nucleotide polymorphism rs1128446 in gene encoding the endogenous thioredoxin regulator TXNRD1 with the risk of CS. A total of 825 unrelated individuals from Central Russia were included for this study: 375 patients with CS (216 males, 159 females; 59.44±0.51 years old) and 450 healthy controls (249 males, 201 females, 61.69±0.38 years old). Genotyping was performed using TaqMan-based PCR. To analyze the associations of genotypes with the risk of diseases, a log-additive regression model was used. All calculations were performed relative to the minor allele; corrections for gender and age have been introduced. SNP rs1128446 TXNRD1 was associated with an increased risk of CS (OR=1.89; 95% CI=1.48-2.43; P<0.0001). Bioinformatic analysis revealed a high regulatory potential of this SNP in tissues of the cardiovascular system. Thus, for the first time, the association of rs1128446 TXNRD1 with the development of CS was revealed.

In this study, we investigated whether polymorphisms g.15661G>T (ADIPOQ), p.A222V (MTHFR), p.Q192R (PON1), p.K23E (KCNJ11), g.53341C>T (TCF7L2), p.V109D (ITLN1) and p.P12A (PPARG) are associated with obesity in the Kyrgyz population. We genotyped 245 nonrelated adults Kyrgyz individuals. 130 patients (male - 65 (50,0%), female - 65 (50,0%) with obesity and 115 non-obese control subjects (male - 62 (53,9%), female - 53 (46,1%). Genotyping of single-nucleotide polymorphism was performed by PCR-RFLP method. Analysis of intergenic interactions conducted with MDR v.3.0.2 program. Тhe V allele and the VV genotype of the p.A222V locus (MTHFR), as well as the K allele and the KK genotype of the p.K23E locus (KCNJ11) increase risk of obesity in the Kyrgyz population. Subjects having the VV genotype of p.A222V locus (MTHFR) and KK genotype of the p.K23E locus (KCNJ11) had 3-fold [OR = 3,49 (1,44-8,45); p = 0,001] higher risk of developing compared with subjects carrying neither of these genotypes.