Objective. To reveal the genetic markers that may predict the efficiency of therapy for rheumatoid arthritis (RA).
Subjects and methods. The study enrolled 104 patients (93 women and 11 men) (mean age 53.38+13.55 years). The duration of RA averaged 9.18+8.97 years. The patients were treated with basic anti-inflammatory drugs (BAIDs): 69.23% took methotrexate (MT), 10-17.5 mg/week; 30.77% received sulfasalazine, 2 g/day. Therapeutic effectiveness was evaluated using the European League Against Rheumatism (EULAR) criteria following 24 weeks. Clinical and laboratory parameters were similar in MT- and sulfasalazine-treated patients. The patients groups showing the varying efficacy of BAIDs were analyzed from the similar cutoffs of polymorphisms of the same cytokine genes.
Results. The study indicated that some patients with certain combinations of allelic variants of promoter regions of cytokine genes had no benefits from BAID therapy. There was a preponderance of alleles in the genes associated with the high production of IL-1, the low generation of IL-6, and the low elaboration of cytokines with anti-inflammatory activity in the group of patients unresponsive to the basic therapy. The patients having many benefits from the performed treatment showed a predominance of alleles associated with the high production of IL-6 and the low generation of IL-1, with a tendency towards an increase in the frequency of alleles in the IL-1 and IL-10 genes that ensured a high elaboration of anti-inflammatory cytokines.
Conclusion. The findings suggest that the effect of basic anti-rheumatic therapy with methotrexate or sulfasalazine largely depends on the cytokine genotype of a patient. Analysis of appropriate factors is likely to be used in rheumatological care.

Objective: to study an association of leptin (LEP) A19G polymorphism and leptin receptor (LEPR) Gln223Arg AND Lys109Arg polymorphisms with the predilection for postmenopausal osteoporosis (OP).
Subjects and methods. PCR analysis was used to examine the polymorphisms among 428 women (254 patients with OP and 174 healthy women). The anthropometric, densitometric, and biochemical markers of bone remodeling and standard clinical and biochemical parameters were studied.
Results. Statistically significant differences were found in the distribution of the genotypes of LEP A19G polymorphism between the women with OP and the controls (χ2 = 9.41; p = 0.009). In the patients with OP, the 19GG genotype frequency was significantly higher than that in the controls [OR = 2.0; 95% confidence interval (CI) 1.13-3.52 (p = 0.011)]. LEP 19GG genotype carriers were found to have lower mineral bone density (MBD) of the femoral neck than heterozygotes (p = 0.06). In LEPR 223GlnArg heterozygotes, the mean MBD of the trochanter and whole hip was statistically significantly lower than that in patients with the genotype 223ArgArg (p = 0.013). 223GlnGln carriers were taller than 223GlnArg ones (p = 0.04). There were no associations of the clinical and biochemical parameters with the polymorphisms studied.
Conclusion. Our study confirmed the role of LEP A19G and LEPR Gln223Arg polymorphisms as important candidate genes involved in the formation of a predilection for OP.

Objective: to study associations between the lesion of the heart and aorta and other clinical manifestations and the characteristics of ankylosing
spondylitis (AS).
Subjects and methods. Three hundred and forty-four patients under 60 years of age with a valid diagnosis of AS without concomitant heart
disease, followed up at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, in 2005-2008, were examined. Of
them, 64 (18.6%) patients had at least one attack of uveitis during the disease; 280 had never uveitis. During the disease, peripheral
arthritis occurred in 160 (46.5%) patients; 184 (53.5%) had axial AS. All the patients underwent ECG; 101 had EchoCG (27 with uveitis
and 74 without uveitis, 63 with arthritis and 38 without arthritis).
Results. Forty-four patients were found to have cardiac conduction disturbances (atrioventricular or left bundle-branch block); of
them 14 (31.8%) and 30 (68%) had uveitis and peripheral arthritis, respectively. Out of the 300 individuals without conduction disturbances,
50 (16.7%) and 130 (43%) had the above conditions (p = 0.01 and 0.003, respectively). Cardiac structural changes
(aortic thickening/dilatation, subaortic bump, aortic and/or mitral leaflet thickening) were revealed in 45 patients; among them 21
(46.7%) and 34 (75%) had uveitis and arthritis, respectively; of the 56 patients without EchoCG changes, 6 (10.7%) and 29 (51%)
had the above conditions (p = 0.0001 and 0.02, respectively). On the other hand, conduction disturbances were noted in 15 (23.4%)
of the 64 patients with uveitis and in 29 (10.3%) of the 280 patients without this condition; p = 0.006; in 30 (19%) of the 160
patients with peripheral arthritis and in 14 (7.6%) of the 180 patients without arthritis; p = 0.003. Aortic and valvular changes were
detected in 16 (59.2%) of the 27 patients with uveitis and in 28 (37.8%) of 74 without this condition; p = 0.04; in 36 (57%) patients
with arthritis and in 9 (23%) of the 38 without arthritis; p = 0.018. There were no significant differences in the parameters of
inflammatory activity between the groups.
Conclusion. In patients with AS, cardiac lesion was significantly more frequently in the presence of uveitis and peripheral arthritis; uveitis
and peripheral arthritis were significantly more common in patients with AS-induced cardiac changes.

Objective: to estimate the levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-α), and soluble TNF-α receptor type 1 (sTNF-R1) in patients with antiphospholipid syndrome (APS) and their association with cardiovascular pathology. Subjects and methods. Ninety-six patients, including 52 with primary APS and 44 with systemic lupus erythematosus and APS, were examined. A control group comprised 29 individuals without the signs of autoimmune disease. The levels of hsCRP, IL-6, TNF-α, sTNF-R1, antiphospholipid antibodies, and plasma lipids were studied; ultrasonography measuring the carotid intima-media complex (IMC), electrocardiography (ECG), echocardiography, and Holter ECG monitoring were made.
Results. The concentrations of hsCRP, IL-6, TNF-α, and sTNF-R1 were significantly higher in the patient groups than in the controls (p < 0.05). Elevated sTNF-R1 concentrations were more common in angina pectoris than in its absence (OR = 2.13; 95% CI [1.51; 2.99]; p < 0.001). In patients with damage to the valvular apparatus, IL-6, TNF-α, and sTNF-R1 concentrations were significantly higher than those in patients without the defects (p = 0.02, 0.02, and 0.01, respectively). The levels of TNF-α and sTNF-R1 were significantly higher in hypertensive patients than those in non-hypertensives (p = 0.002 and p < 0.001; respectively). The blood concentration of TNF-α was significantly higher in patients having the risk factors and subclinical signs of atherosclerosis that that in those without the signs and risk factors of atherosclerosis (p < 0.05). Analysis showed a direct correlation between the levels of TNF-α, hsCRP, IL-6, and sTNF-R1 and an inverse correlation of those of IL-6 and TNF-α with the duration of posttrombosis (p < 0.05). A correlation was found between the concentrations of TNF-α and sTNF-R1, and IMC of the great arteries, as well as the cumulative coronary risk (p < 0.05). Conclusion. In patients with APS, the levels of all the test markers were significantly higher than those in the controls. An association was revealed between the values of TNF-α and sTNF-R1 and the risk factors and subclinical signs of atherosclerosis.

The blood levels of native DNA antibodies, rheumatoid factor, IgG and IgM cardiolipin antibodies, and free and protein-bound oxyproline were compared in subjects with and without various cardiac dysplasias in the presence and absence of autonomic dysfunction. There were differences in these parameters between the study groups.

Objective: To study the effect of type II collagen peptide (CB12-2) that is able to induce the collagen decomposition in the knee articular cartilage explants, which activates matrix metalloproteinase (MMP) and articular chondrocyte differentiation.
Material and methods. Human cartilage explants were cultured in the presence of CB12-2 (amino acid residues 195-218) at a concentration of 10 μM. Type II collagen decomposition was evaluated by enzyme immunoassay. Immunohistochemical assay of type X collagen (C0L10A1) used frozen cartilage sections. Apoptotic activity was measured by terminal deoxynucleotidyl transferase-mediated dUPTnick end-labeling method (TUNEL). Gene expressions were determined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR).
Results. CB12-2 at high, but naturally occurring concentrations (10 μM) induced type II collagen decomposition by collagenase in the cartilage explants from a healthy individual. The peptide caused an increase in the expression of MMP 13, 1, 9, MT1-MMP, and the genes associated with the differentiation of embryo chondrocytes in the growth plate - transforming growth factor (TGF) β1/2, sex-determining region Y-box 9 (Sox9), Indian hedgehog (Ihh), parathyroid hormone-related peptide (PTHrP), fibroblast growth factor (FGF-2); a marker for proliferation of cyclin B2 and cytokines of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1Я). At the same time the increased expression of the chondrocyte hypertrophy marker C0L10A1 was accompanied by enhanced staining for type X collagen in the frozen cartilage sections whereas the number of TUNEL-positive cells increased in the cartilage surface area as the expression of the apoptotic marker caspase 3 became higher.
Conclusion. This study has shown that the induction of collagenase activity by CB12-2 in the human articular cartilage chondrocytes is attended by terminal differentiation/hypertrophy of these cells. The terminal differentiation of chondrocytes may be one of the mechanisms of chondrolysis in osteoarthrosis since it naturally occurs not only in endochondrial ossification, but also in the development of pathology.