Molecular characteristics of patients with glycosaminoglycan storage disorders in Russia.

Background: The mucopolysaccharidoses (MPSs) are rare genetic disorders caused by mutations in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). In this study, we analyzed a total of 48 patients including MPSI (n=6), MPSII (n=18), MPSIIIA (n=11), MPSIVA (n=3), and MPSVI (n=10).

Methods: In MPS patients, urinary GAGs were colorimetrically assayed.

Genetic analysis of 17 children with Hunter syndrome: identification and functional characterization of four novel mutations in the iduronate-2-sulfatase gene.

Mucopolysaccharidosis type II (MPS II) is a rare X-linked disorder caused by alterations in the iduronate-2-sulfatase (IDS) gene. In this study, IDS activity in peripheral mononuclear blood monocytes (PMBCs) was measured with a fluorimetric enzyme assay. Urinary glycosaminoglycans (GAGs) were quantified using a colorimetric assay.

Genetic background of juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatologic disease in children. JIA is a group of disorders that share the clinical manifestation of chronic joint inflammation. The human leukocyte antigen region (HLA) seems to be a major susceptibility locus for JIA that is estimated to account for 17% of familial segregation of the disease.

[Contribution of non-HLA genes to juvenile idiopathic arthritis susceptibility].

Juvenile idiopathic arthritis (JAL4) is the most common chronic rheumatologic disease in children. JIA is a group of disorders that share the clinical manifestation of chronic joint inflammation. The Human Leukocyte Antigen region (HLA) seems to be a major susceptibility locus for JIA that is estimated to account for 17% of familial segregation of the disease.

A variant of the Il2ra / Cd25 gene predisposing to graves' disease is associated with increased levels of soluble interleukin-2 receptor.

Alpha-subunit of the IL-2 receptor (IL-2Rα) encoded by the IL2RA/CD25 gene binds IL-2 that plays a pivotal role in the regulation of T cell function. Levels of a soluble form of IL-2Rα (sIL-2Rα) lacking the transmembrane and cytoplasmic domains were shown to be increased in several autoimmune diseases including Graves' disease (GD). Recent studies showed association between the IL2RA/CD25 gene variants and several autoimmune diseases including GD.

The -112G>A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves' disease in subsets of patients with elevated levels of immunoglobulin E.

The human secretoglobin 3A2 (SCGB3A2) gene encoding secretory uteroglobin-related protein 1 (UGRP1) resides on the chromosome region 5q31-33 that harbors a susceptibility locus to several autoimmune and inflammatory diseases, including asthma and Graves' disease (GD). Recently, association between the marker rs1368408 (-112G >A), located in the promoter region of the SCGB3A2 gene, and susceptibility to GD was found in Chinese and UK Caucasians. The study aim was to evaluate whether this polymorphism confers GD susceptibility in a large population cohort comprising 1,474 Russian GD patients and 1,619 controls.

Loss-of-function mutations E6 27X and I923V of IFIH1 are associated with lower poly(I:C)-induced interferon-β production in peripheral blood mononuclear cells of type 1 diabetes patients.

Melanoma differentiation-associated 5 (MDA5), a product of the IFIH1 gene, is responsible for sensing double-stranded viral double-stranded RNA (RNA). In this study, we showed a significant association of two rare IFIH1 variants, rs35744605 (E627X) and rs35667974 (I923V), with decreased risk of type 1 diabetes (T1D) in a Russian population (for the allele X627, odds ratio [OR] = 0.39, 95% confidence interval [95% CI] = 0.

The 262T>C promoter polymorphism of the catalase gene is associated with diabetic neuropathy in type 1 diabetic Russian patients.

Objective: Oxidative stress plays an important role in the development of diabetic neuropathy (DN). Antioxidant enzymes reduce enhanced oxidative stress in the peripheral nerve. Genetic variations within the antioxidant genes therefore could be implicated in the pathogenesis of DN.

Genetic analysis and functional evaluation of the C/T(-318) and A/G(-1661) polymorphisms of the CTLA-4 gene in patients affected with Graves' disease.

In this study, we evaluated the A/G(-1661), C/T(-318), A/G49 and A/G6230 single nucleotide polymorphisms (SNPs) of the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene for association with Graves' disease (GD) in 126 Russian simplex families. The conditional TDT analysis revealed significant overtransmission of the A(-1661)G(-318) haplotype (P = 0.033) and undertransmission of the GT haplotype (P = 0.

The TAF5L gene on chromosome 1q42 is associated with type 1 diabetes in Russian affected patients.

Type 1 diabetes (T1D) is a multifactorial autoimmune disease, with strong genetic component. Several susceptibility loci contribute to genetic predisposition to T1D. One of these loci have been mapped to chromosome 1q42 in UK and US joined affected family data sets but needs to be replicated in other populations.

Lack of association between genetic markers on chromosome 16q22-Q24 and type 1 diabetes in Russian affected families.

Aim: To evaluate whether the T1D susceptibility locus on chromosome 16q contributes to the genetic susceptibility to T1D in Russian patients.

Method: Thirteen microsatellite markers, spanning a 47-centimorgan genomic region on 16q22-q24 were evaluated for linkage to T1D in 98 Russian multiplex families. Multipoint logarithm of odds (LOD) ratio (MLS) and nonparametric LOD (NPL) values were computed for each marker, using GENEHUNTER 2.

Evaluation of IDDM8 susceptibility locus in a Russian simplex family data set.

Type 1 diabetes (T1D) susceptibility locus, IDDM8, has been accurately mapped to 200 kilobases at the terminal end of chromosome 6q27. This is within the region which harbours a cluster of three genes encoding proteasome subunit beta 1 (PMSB1), TATA-box binding protein (TBP) and a homologue of mouse programming cell death activator 2 (PDCD2). In this study, we evaluated whether these genes contribute to T1D susceptibility using the transmission disequilibrium test of the data set from 114 affected Russian simplex families.

Screening of SNPs at 18 positional candidate genes, located within the GD-1 locus on chromosome 14q23-q32, for susceptibility to Graves' disease: a TDT study.

Graves' disease (GD) is a complex autoimmune thyroid disorder with a strong genetic component. Genome-wide screens resolved several susceptibility loci that contribute to the development of GD. One of the susceptibility loci (GD-1 locus) was mapped on chromosome 14q31.

Confirmation of a susceptibility locus for diabetic nephropathy on chromosome 3q23-q24 by association study in Russian type 1 diabetic patients.

Family-based studies and segregation analyses suggest that inherited factors play a significant role in susceptibility to diabetic nephropathy (DN). Moczulski et al. [Diabetes 47 (1998) 1164-1169] found a susceptibility locus for DN in type 1 diabetes covering a 20cM region on chromosome 3q, with a peak of linkage close to the angiotensin II type 1 receptor (AT1) gene.

Evidence for a type 1 diabetes susceptibility locus (IDDM10) on chromosome 10p11-q11 in a Russian population.

Around 20 susceptibility loci for type 1 diabetes mellitus (T1DM) have been mapped. One of these loci, IDDM10, was found on chromosome 10p11-q11. Here, we investigated whether the IDDM10 locus contributes in the susceptibility to T1DM in a Russian family dataset.

A new type 1 diabetes susceptibility locus containing the catalase gene (chromosome 11p13) in a Russian population.

Background: Oxidative stress is involved in the origin of type 1 diabetes. Low efficiency of the scavenging antioxidant system has been shown to be related to the pathogenesis of the disease. This, therefore suggests that genes encoding catalase and other antioxidant enzymes may implicate in the development of type 1 diabetes.

Further studies of genetic susceptibility to Graves' disease in a Russian population.

Background: Graves' disease (GD) is a polygenic autoimmune thyroid syndrome. Some of the genes implicated in its pathogenesis may encode thyroid-stimulating hormone receptor (TSHR) and estrogen receptors 1 (ESR1) and 2 (ESR2). We examined dinucleotide repeat polymorphisms in the ESR1 and ESR2 genes and D727E amino acid substitution in the TSHR gene for possible association with GD in a Russian population.

Polymorphisms in the Mn-SOD and EC-SOD genes and their relationship to diabetic neuropathy in type 1 diabetes mellitus.

Background: Oxidative stress, resulting in a marked increase in the level of oxygen free radicals (OFR), has been implicated in the etiology of diabetic neuropathy (DN). Antioxidant enzymes may protect against the rapid onset and progression of DN, by reducing the excess of OFR and peroxide. Mutations and polymorphisms in the genes encoding such enzymes may therefore result in predisposition to DN.

CTLA4 gene polymorphisms are associated with, and linked to, insulin-dependent diabetes mellitus in a Russian population.

Background: The association between the human cytotoxic T lymphocyte-associated antigen-4 (CTLA4) gene and insulin-dependent diabetes mellitus (IDDM) is unclear in populations. We therefore investigated whether the gene conferred susceptibility to IDDM in a Russian population. We studied two polymorphic regions of the CTLA4 gene, the codon 17 dimorphism and the (AT)n microsatellite marker in the 3' untranslated region in 56 discordant sibling pairs and in 33 identical by descent (IBD) affected sibships.

Genetic determinants of Graves disease.

Basedow-Graves disease is an autoimmune thyroid syndrome. Genetic factors contribute to the pathogenesis of Graves disease, and current findings confirm that a number of genes may be involved in the development of autoimmune thyrotoxicosis. At present three loci, namely human leukocyte antigen (HLA, 6p21.

Complex association analysis of graves disease using a set of polymorphic markers.

Graves disease is complex autoimmune thyrotoxicosis. A number of genes may contribute to the development of the disorder. Some of them may be genes that encode cytotoxic T-lymphocyte-associated serine esterase-4 (CTLA4), subunit 2 of large multifunctional protease (LMP2), thyroid-stimulating hormone receptor (TSHR), and interleukin 1 receptor antagonist (IL1RN).