Juvenile idiopathic arthritis patients and their skeletal status: possible role of vitamin D receptor gene polymorphism.

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; Ca(2+): 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.

[Correlation of metabolic syndrome clinical signs and genetic determinants at children with obese].

UNLABELLED: The aim of the work was to study the clinical and genetic factors at children with obese that predispose to the development of MS, and the development of algorithm for generating risk of MS. MATERIALS AND METHODS: Two comparable age and sex groups of children--148 children with obesity and 46--with normal body weight. We assessed anthropometric indices, blood pressure (BP), lipid profile, carbohydrate metabolism, the level of uric acid. 83 children with obesity were genotyped for polymorphisms: I/D gene ACE, G-75A ApoA1, S19W ApoA5, Sstl ApoC3, E2/E3/E4 ApoE and W/R ADRB3. RESULTS: 98,0% of children had abdominal obesity. In 35,8% was identified high blood pressure. In 47,4% was diagnosed hypo-alpha cholesterolemia and/or hypertriglyceridemia (HTG). In 21,0% of children was identified hyperglycemia. 25,7%were suffered from hyperuricemia. Among the genotyped children 57,0% of homo-and heterozygous carriers of D allele ACE gene had high blood pressure. More than half of the holders of 19W-allele ApoA5 (68,5%),--75A-allele of ApoA1 (56,0%), 52-allele of the gene ApoC3 (53,0%), E4-ApoE gene (85,7%), in the heterozygous state had metabolic TG and/or HDL. In 60,3% of the carriers W/W genotype of ADRB3 gene revealed a combination of hyperglycemia with hyperinsulinemia and/or TG. CONCLUSION: As a result of, aiming aimed at early detection of the major manifestations of MS clinical and genetic study was revealed stable combination of constitutional, metabolic and molecular-genetic factors. Based on these data was developed algorithm for forming groups at risk of MS and individual tactics to prevent and/or therapy.

[Epidemiology and risk factors of chronic renal diseases: a regional level of the problem].

AIM: Assessment of chronic renal disease (CRD) prevalence and morbidity rate and approaches to early CRD in one of the regions of the RF (Tyva Republic). MATERIAL AND METHODS: A population study in the Tyva Republic performed from 01.07.2003 to 30.06.2004 included patients with glomerular filtration rate (GFR) < 30 ml/min, nephrosclerosis signs at autopsy, terminal GFR < 30 ml/min, on replacement renal therapy (RRT). CRD prevalence and morbidity were estimated (stage IV-V). Examination of 374 Tyva citizens was made for estimation of early CRD and risk factors of developing CRD (the sectional study). The participants of the sectional study were examined clinically and biochemically with measurement of albuminuria, calculation of urine albumin/creatinine (ACR) and study of some molecular-genetic characteristics. RESULTS: Prevalence of CRD stage IV-V in Tyva population was 493 cases per million, prevalence of RRT--126 cases per million. Elevated ACR was found in 4.7% of healthy subjects and 15.9% of hypertensive subjects. Initial lowering of GFR occurred in some healthy subjects and in 1 of 12 hypertensive patients. Significant predictors of albuminuria were serum albumin concentration (p < 0.00001), GFR (p < 0.0002), a male sex (p < 0.004), diabetes mellitus (DM) (p = 0.0057) and left ventricular myocardial mass index (p = 0.0253). GFR depended significantly on age (p < 0.000001), male sex (p < 0.000001), uric acid concentration in the serum (p < 0.000001), presence of DM (p = 0.000019), ACR (p = 0.0059), diastolic pressure (p = 0.0347), triglyceridemia (p = 0.0369). Citizens of Tyva had more frequently than citizens of other regions of Russia IlI-genotype of angiotensin 1-converting enzyme (ACE) (p < 0.0001), T-allele of methylentetrahydrofolatereductase (p < 0.0001), E3-allele of gene of apoprotein E (p < 0.0001). Prevalence of aa, ab, bb genotypes of eNO-synthetase was 82.3%, 15% and 2.7% in the group of Tyva examinees vs 62, 31 and 7% in European Russians (p < 0.01). CONCLUSION: Prevalence of both early and advanced stages of CRD among population of Tyva Republic is rather high. CRD morbidity may depend, besides conventional risk factors, some genetic specific features. Screening studies require continuation for early detection of CRD and timely planning of therapeutic and preventive measures.

Methylenetetrahydrofolate reductase gene polymorphism as a risk factor for diabetic nephropathy in IDDM patients.

A missense mutation in the methylenetetrahydrofolate reductase gene (MTHFR), C677T, results in a thermolabile variant with reduced activity. Elevated levels of homocysteine have been recognized as a risk factor for vascular disease. Insulin-dependent diabetes mellitus (IDDM) is characterized by a higher prevalence of vascular complications. We analyzed the frequency of C677T MTHFR in IDDM and control groups. The genotype distribution did not differ between control subjects (n = 297) and IDDM patients (n = 392) (chi(2) = 5.413, df = 2, P > 0.05). The MTHFR T677T genotype was found significantly more frequently in IDDM patients with diabetic nephropathy (0.216) compared with the IDDM patients without nephropathy (0.056); the odds ratio was 2.635 (95% CI 1.768-3.927). Thus, we suggest that the T677T genotype of the MTHFR gene is an independent risk factor for diabetic nephropathy in IDDM.