The aim of this study was to assess the role of simple clinical and laboratorial markers for prediction of low bone mineral density (LBMD < -2 SD) in children with juvenile idiopathic arthritis (JIA). Low weight and linear growth (<10% and 25%), BMI < 16.6, MD VAS > 5.0, DAS > 2.9, DAS28 > 4.2, JADAS 10 > 15.6, JADAS 27 > 15.1, CDAI > 18.1, Steinbrocker's functional class > 2, systemic arthritis, corticosteroid treatment, arthritis duration > 4.5 years, number of active joints > 5, number of painful joints > 9, morning stiffness > 90 minutes, parental overall JIA activity (VAS) > 5.8, ESR > 16 mm/h, CRP > 22.6 mg/l were associated with increased risk of LBMD in JIA children. Among metabolic markers Ca total < 2.42 mmol/l and Pi > 1.59 mmol/l also increased the possibility of LBMD. Our data can help to identify the JIA patients at risk for LBMD and to suggest the indications for densitometry evaluation of JIA children.

We evaluated bone mineralization and metabolism changes related to vitamin D receptor (VDR) polymorphic genotypes in children with juvenile idiopathic arthritis. One hundred and ninety eight children (82 boys and 116 girls) were included in our study. Bone mineral density (BMD) was measured by lumbar spine DXA. Osteocalcin, CTX, parathyroid hormone, total and ionized calcium, inorganic phosphate, total alkaline phosphatase activity was utilized for assessment of bone metabolism. Molecular testing: TaqI (rs731236) and Cdx2 (rs11568820) polymorphisms of VDR were detected by RFLP. No differences in TaqI and Cdx2 haplotypes, genotypes and alleles distribution related with normal and low BMD (Zscore <−2SD) were found. Children with low linear growth (<10th percentile) had more allele T-contained genotypes of TagI VDR (p = 0.037), compare with medium or high linear growth children. Children with high linear growth (>90th percentile) had the highest frequency of allele A-contained genotypes (GA+AA) of Cdx2 VDR (p = 0.009). Girls with TT TaqI VDR, who never been treated by glucocorticoides had lower BMD-Zscore than C allele carriers (TT = −0.94SD [IQR: −2.1;−0.5], TC+CC = −0.62SD [IQR: −1.26;0.39], p = 0.03). Girls with Tanner I with TT had higher total and ionized Ca level than carriers of C allele (Ca: TT = 2.43 ± 0.15 mmol/l, TC+CC = 2.28 ± 0.2 mmol/l, p = 0.024; Ca2+: TT = 1.15 ± 0.08 mmol/l, TC+CC = 1.06 ± 0.13 mmol/l, p = 0.026). Presence of TT genotype negatively correlated with BMD-Zscore (r = −0.28, p = 0.04), and positively with frequency of LBMD (r = 0.3, p = 0.037). Boy with GG Cdx2 genotype had lower total Ca (GG = 2.3 ± 0.17 mmol/l, GA+AA = 2.43 ± 0.17 mmol/l, p = 0.004) compare with carriers of A allele. Pubertal boys (Tanner IV–V) with GG had higher CTX (GG = 1.75 ± 0.11 ng/ml, GA+AA = 1.06 ± 0.07 ng/ml, p = 0.04. TT genotype of TaqI and GG genotype of Cdx2 VDR is a negative factor impact bone mineralization metabolism and linear growth.

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease associated with impaired immune system performance. The specific features of JIA may be genetically determined.Objective: to assess JIA activity in children with vitamin D receptor (VDR) gene ApaI and BsmI polymorphism genotypes.Subjects and methods. The investigation enrolled 71 patients with JIA. When included in the investigation, all the patients were in an active state of disease. JIA activity was assessed using the most commonly used clinical and laboratory indicators, including the Ritchie articular index (RAI), JADAS10, JADAS27, JADAS71, CDAI, DAS, and DAS28. Molecular genetic studies determined VDR gene ApaI and BsmI polymorphisms by polymerase chain reaction, followed by restriction analysis.Results. The boys who were carriers of a bb BsmI polymorphic marker in the VDR gene had a significantly higher activity of JIA measured by RAI (p=0.03), DAS (p<0.05), JADAS10 (p=0.04), JADAS27 (p=0.04), and JADAS71 (p=0.04) than those who were carriers of B allele (BB + Bb genotypes).Conclusion. The carriage of the VDR gene bb BsmI genotype of the polymorphic marker is associated with high JIA activity, which may be regarded as a marker of poor prognosis in boys with JIA.

Background Juvenile idiopathic arthritis (JIA) – chronic articular disease related to immune system dysfunctions. JIA course and complications have genetic background. Objectives We evaluated features of JIA and related bone mineralization and metabolism changes with VDR polymorphic genotypes in children with JIA. Methods 71 children with active JIA were included in our study. For assessment of JIA activity we used onset age, duration of morning stiffness, number of active joints, white blood cells (WBC) count, Westergren erythrocyte sedimentation rate (ESR), C-reactive protein. Physician global assessment (PGA) of disease activity, measured on a 10-cm visual analog scale (VAS) where 0 = no activity and 10 = maximum activity; parent/patient global assessment of well-being, measured on a 10-cm VAS where 0 = very well and 10 = very poor. We utilized combined indexes for assessment disease activity – JADAS10, JADAS27, JADAS71, CDAI, DAS and DAS28 were utilized. Bone mineralization was measured in all children by dual-energy X-ray absorptiometry (DXA) of lumbar spine (LS) at L1-L4 (Hologic QDR 4500C densitometer with reference pediatric database). Densitometry parameters, such as bone area (BA, cm2), bone mineral content (BMC, grams) and bone mineral density (BMD, measured in grams/cm2 and in Z score, SD) were all evaluated. Low bone mineral density (LBMD) for chronological age was defined by Z score < 2 SD, according to the recommendation of the International Society for Clinical Densitometry, 2007. For assessment of bone metabolism the following measures were used: osteocalcin (bone gla-protein, a marker of osteosynthesis), carboxyterminal telopeptide of type I collagen (CTX -products of collagen I type degradation and a marker of bone resorption) and parathyroid hormone (PTH) by routine imunoenzyme methods. Also levels of total calcium (Ca), ionized calcium (Ca++), inorganic phosphate (Pi) and total alkaline phosphatase (ALP) were determined. Molecular testing – ApaI and BsmI polymorphisms of VDR gene polymorphisms were detected by restriction fragment length polymorphism. Results There were no significant differences of ApaI and BsmI polymorphic genotypes, alleles and haplotypes distribution between children with normal and low BMD. BsmI polymorphism was associated with arthritis activity only in boys and ApaI polymorphism was related to JIA activity only in girls. Girls with AA genotypes ApaI VDR had higher BMD and BMD-Zscore compare with aa and Aa carriers respectively. Boys with B allele (BB+Bb genotypes) BsmI VDR had lower RAI, DAS and JADAS 10. The same changes were observed in JADAS 27 (p=0,04) and JADAS 71 (p=0,04). Conclusions differences in JIA activity and bone mineralization related to VDR genetic polymorphisms confirms the multi-potential role of vitamin D which regulates on immune system and bone metabolism. Disclosure of Interest None Declared

Objective. To evaluate G-75A and C+83T polymorphisms of apolipoprotein A1 gene and Q192R polymorphism of paraoxonase 1 gene and their association with blood pressure and lipid levels in patients with abdominal obesity. Design and methods. We examined 222 obese patients (57 males and 165 females), residents of St Petersburg, Russian Federation. Results. High incidence of arterial hypertension (61 %) and dyslipidemia of different types was revealed. The frequency of different alleles of apolipoprotein A1 and paraoxonase 1 genes was analyzed. The results of gene-gene interactions and their associations with blood pressure, obesity and lipids profiles are presented.

This study describes bone metabolism in children withjuvenile idiopathic arthritis (JIA), association between disturbances of bone metabolism with inflammatory activity, juvenile arthritis disease course and therapy in 198 children. Low bone mineral density (BMD) for chronological age was detected by dual-energy X-ray absorptiometry of lumbar spine L1-L4 (densitometer Hologic QDR 4500C, with pediatric reference database) than Z -score < -2 SD in 36 children (18,2%), in 18 girls (15,5%) and in 18 boys (21,9%). Girls with low BMD received glucocorticoids (GCS) in 66,7 % cases, and girls with normal BMD received it in 26,5% cases (р=0,002). Girls with low BMD had lower height, weight, earlier age of disease onset and higher clinical and laboratory parameters of arthritis activity. Girls with low BMD had higher osteocalcin and tendency to decreased parathyroid hormone levels compared to the girls with normal BMD. Children who received GCS had specific stereotypic changes: boys had significantly lower bone mineral density and total Ca and girls had significantly lower bone mineral content and BMD (g/cm2 and Z-score), total Са, non-organic phosphate and total alkaline phosphatase activity. Patients with systemic arthritis had significantly lower mineralization and bone metabolism turnover compared to children with oligoarticular and polyarticular JIA subtypes. Independent predictors of skeletal mineralization were age onset f JIA (р<0,0001), duration of the disease (p<0,0001), hemoglobin level (р=0,004), total calcium level (р=0,024), a2-globulins level (р=0,046). Independent predictors of low BMD were physician’s assessment VAS (р=0,024), C-reactive protein (р=0,04), inorganic phosphate (р=0,05). Systemic glucocorticoids exposure elevated the risk of low BMD for chronological age realization in JIA patients (OR=1,96, 95%CI=0,76-5,05). Enhanced risk of low BMD was in polyarthicular (OR=2,53, 95%CI=0,66-9,65) and systemic JIA (OR=3,16, 95%CI=0,73-13,76). Thus, parameters of inflammation have negative influence on bone metabolism velocity, linear growth and accordingly bone mineralization. Described factors explain heterogeneity of mineralization disorders.

Background. To detect sixteen cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations most common to Russian populations in children with severe asthma (SA). Patients and Methods. S A group included 59 children aged 4-17 years old (43 boys and 16 girls). Cystic fibrosis (CF) group included 27 children aged 5-17 years old with a primary diagnosis of CF (15 boys and 12 girls). We used two kits developed by Center for M olecular Genetics (Moscow): «CF-5» kit (G542X, W1282X, N1303K, 3849+10kbC>T, R334W) and «CF-11» kit (del21 kb, F508del, I 507del, 1677delTA, 2143delT, 2184insA, 394delTT, 3821delT, L138ins, 604insA, 3944delTG). Results. I n the group of children with CF, the frequency a major mutation F508del was 85% (41% with genotype F508del/ F508del, 29% with genotype F508del/nomal and 15% with compound genotype F508del/others). I n 15% of the cases, there were identified some other mutations of the CFTR gene: N1303K, 394delTT, 2143delT, CFTRdele2, 3 (21kb). The rest 7% of the cases were not clarified. We have found neither «mild» nor «severe» the mutations of CFTR gene in the S A group. Conclusion. This study failed to show an association of mutations of CFTR gene with severe asthma in children.

Methods We included 196 JIA children, 81 boys and 115 girls. Bone mineralization parameters were detected by dual-energy X-ray absorptiometry of lumbar spine L1-L4. Bone biochemical markers were osteocalcine, C-terminal telopeptides (CTT), parathyroid hormone (PTH), Ca, Ca, P, total alkaline phosphatase (TAP) activity. We have detected Sp1 (rs1800012) and -1997G/T (rs1107946) polymorphisms in type I alpha-1 chain collagen gene (COL1A1).

QDR 4500С, оснащённый педиатрической референсной базой) при Z-sсоrеThis study describes bone metabolism in children withjuvenile idiopathic arthritis (JIA), association between disturbances of bone metabolism with inflammatory activity, juvenile arthritis disease course and therapy in 198 children. Low bone mineral density (BMD) for chronological age was detected by dual-energy X-ray absorptiometry of lumbar spine L1-L4 (densitometer Hologic QDR 4500C, with pediatric reference database) than Z -score

The aim of our study is researching influence of vitamin D and osteocalcin polymorphic gene markers in people, who lived in Blockaded Leningrad in 1941-1944 and detecting “critical age” of peak bone mass formation in these people. We included in our study 48 peoples, 13 males and 35 females. Osteodensitometry of lumbar spine (L1-L4) and proximal hip was used by dualenergy X-ray absorptiometer GE Lunar Prodigy Vision 6. Molecular diagnostic researching are: detecting ApaI, TagI vitamin D receptor (VDR) and HindIII osteocalcin gene polymorphism by polymerase chain reaction with restriction assay. Women with osteopenia of hip neck had significantly higher age in the onset of Blockade, than women without osteopenia. Genotype ТТ and allele Т of TagI, aa genotype of ApaI VDR, genotype hh and allele h of HindIII osteocalcin gene polymorphism will be able as markers of genetic predisposing to osteoporosis in people, who lived in Blockaded Leningrad.

The aim of our study is researching influence of vitamin D and osteocalcin polymorphic gene markers in people, who lived in Blockaded Leningrad in 1941-1944 and detecting “critical age” of peak bone mass formation in these people. We included in our study 48 peoples, 13 males and 35 females. Osteodensitometry of lumbar spine (L1-L4) and proximal hip was used by dualenergy X-ray absorptiometer GE Lunar Prodigy Vision 6. Molecular diagnostic researching are: detecting ApaI, TagI vitamin D receptor (VDR) and HindIII osteocalcin gene polymorphism by polymerase chain reaction with restriction assay. Women with osteopenia of hip neck had significantly higher age in the onset of Blockade, than women without osteopenia. Genotype ТТ and allele Т of TagI, aa genotype of ApaI VDR, genotype hh and allele h of HindIII osteocalcin gene polymorphism will be able as markers of genetic predisposing to osteoporosis in people, who lived in Blockaded Leningrad.

Objective. To assess possible association between PON1 activity, PON1 gene polymorphism, plasma lipid spectrum alterations, and the oxidative stress level in coronary artery disease (CAD) development. Design and methods. 227 male patients with CAD (mean age 46,9 ± 0,5 years), survived myocardial infarction being under 45 years old, and 114 healthy men (mean age 40,0 ± 0,5 years). Plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDLC) levels, and arylestarase PON1 activity have been measured. Plasma malondialdehyde (MDA) concentrations, a lipid peroxidation product, were used as a marker of the oxidative stress levels. Q192R and L55M polymorphisms of the PON1 gene have been identified using PCR-RFLP. Results. CAD patients had significantly higher levels of TC and TG (р = 0,024 and р PON1 gene. RR-homozygotes had significantly lower levels of serum PON1 activity compared to QQ-homozygotes (p = 0,012). Conclusions. Thus, investigation of the PON1 activity together with atherosclerosis risk factors, such as oxidative stress, atherogenic plasma lipid profile and genetic polymorphism, is important for CAD diagnostics and treatment.