Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
19627014 [Promising diagnostic model for systemic lupus erythematosus using proteomic fingerprint t 2009 May OBJECTIVE: To establish a diagnostic model for systemic lupus erythematosus (SLE) using proteiomic fingerprint techology. METHODS: Blood samples were collected from 64 cases of SLE, 30 cases of rheumatoid arthritis (RA), 30 cases of Sjogren's syndrome (SS), 25 cases of systemic sclerosis (SSc), as well as 83 healthy controls. Proteomic spectra of these 232 serum samples were generated by proteomic fingerprint technology. Diagnostic model was established by a machine learning algorithm called decision boosting. The sensitivity and specificity of the diagnostic model was validated with a blinded testing set. RESULTS: Sixty differential protein peaks (P<0.05) between SLE and control subjects were indicated, 28 of them were up regulated and 32 were down regulated in SLE patients. The algorithm identified a cluster pattern segregating SLE from non-SLE with sensitivity of 91% and specificity of 92%. The discriminatory diagnostic pattern correctly identified SLE. A sensitivity of 78% and specificity of 96% for the blinded test were obtained when comparing SLE vs non-SLE. CONCLUSION: This diagnostic model using proteiomic fingerprint techology appears to be a promising tools with high sensitivity and specificity in diagnosis of SLE.
19497928 Arterial compliance in multiple sclerosis: a pilot study. 2010 Feb A reduction in arterial compliance in patients with autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus has been previously reported. It is caused by the effect that systemic inflammation has on the cardiovascular system. Multiple sclerosis (MS), an immune-mediated disease that exclusively affects the central nervous system (CNS), has a significant inflammatory component that is limited to that compartment. The potential effects of its inflammatory mediators in the cardiovascular system are largely unknown. PURPOSE: To examine large (C1) and small arterial compliance (C2) in patients with MS and compare them with healthy age-matched controls. To also determine whether any differences in C1 and C2 indices between participants diagnosed with relapsing remitting MS (RR-MS), secondary progressive MS (SP-MS), and controls exist. METHODS: A total of 26 men and women between the ages of 18 and 64 diagnosed with MS and 25 healthy controls volunteered for this study. Arterial compliance was measured by using pulse contour analysis (PCA), which records and analyzes the blood pressure waveform data from the Arterial Pulse Wave Sensors. RESULTS: Significant differences in C1 and C2 were found between young RR-MS and healthy young controls (P < .05), with the MS group showing lower arterial C1 and C2 compliance. No significant differences (P > .05) were seen for C1 or C2 values between older RR-MS, SP-MS, and healthy controls. CONCLUSION: Arterial compliance is significantly compromised in young individuals with MS, compared with age-matched controls, but not for older individuals, suggesting a systemic effect of an inflammatory process that predominantly affects the CNS.
19237640 Oxidative modifications of S100 proteins: functional regulation by redox. 2009 Sep Several S100 Ca(2+)-binding proteins undergo various post-translational modifications that may alter their intracellular and extracellular functions. S100A8 and S100A9, two members of this family, are particularly susceptible to oxidative modification. These proteins, abundantly expressed in neutrophils and activated macrophages, are associated with acute and chronic inflammatory conditions, including microbial infections, cystic fibrosis, rheumatoid arthritis, and atherosclerosis. They have diverse intracellular roles including NADPH oxidase activation and arachidonic acid transport and can be secreted via a Golgi-independent pathway to exert extracellular functions. Many pro-inflammatory functions have been described for S100A8 and S100A9, but they are also implicated in anti-inflammatory roles in wound-healing and protection against excessive oxidative tissue damage,the latter as a result of their exquisite capacity to scavenge oxidants. Similarly, their genes are induced by proinflammatory (LPS and TNF-alpha) stimuli, but induction is IL-10-dependent, and anti-inflammatory glucocorticoids induce or amplify expression. S100A8 and S100A9 were described recently as damage-associated molecular pattern molecules, which provide a novel, conceptual framework for understanding their functions. However, because of this designation, recent reviews focus solely on their pro-inflammatory functions. Here, we summarize the mounting evidence from functional and gene regulation studies that these proteins may also play protective roles. This review offers an explanation for the disparate, functional roles of S100A8 and S100A9 based on emerging data that post-translational, oxidative modifications may act as a regulatory switch.
19040354 Primary sequence, together with other factors, influence peptide deimination by peptidylar 2009 Feb Enzymes of the peptidylarginine deiminase (PAD) family catalyze the posttranslational deimination of polypeptide-bound arginine residues. Here, we report the selection of peptide substrates by PAD-4, an isoform thought to be involved in the pathogenesis of rheumatoid arthritis. First, we investigated whether PAD-4-mediated deimination is influenced by the nature of amino acid residues flanking the targeted arginine. Using two peptide substrates, residues in positions -2, -1, +1, and +2 relative to the central arginine targeted by PAD-4 were systematically replaced by all natural L-amino acids except cysteine. Each peptide was treated with recombinant human PAD-4 and deimination was analyzed by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. In all four flanking positions, amino acids which positively or negatively influenced deimination were identified. We next designed peptides with expected high or low deimination rates and determined their Km and kcat values. These peptides showed PAD-4 substrate behavior as predicted, demonstrating that residues flanking the targeted arginine are important for deimination. Further truncation of peptide substrates suggested additional effects on deimination by residues outside the -2 to +2 region. Finally, we observed that a methylated lysine residue flanking the targeted arginine influences PAD-4-mediated deimination, also suggesting that posttranslational modifications can affect substrate efficiency.
18484967 Phospholipid compositions of sera and synovial fluids from dog, human and horse: a compari 2009 Aug Alterations of the phospholipid (PL) compositions of body fluids are assumed to be indicative of inflammatory diseases, e.g. rheumatoid arthritis (RA). Recently, we have shown that particularly the phosphatidylcholine/lysophosphatidylcholine (PC/LPC) ratio determined in human synovial fluids (SF) and sera represents a reliable measure of the inflammatory state in RA patients. However, it is not yet clear to what extent the PC/LPC ratio is also affected by nutrition habits. In the present study, the PL and the corresponding acyl chain compositions of human body fluids (SF and serum of RA patients as well as serum from healthy volunteers) are compared with those of two other mammalian species (horses and dogs suffering from degenerative joint diseases as well as healthy controls) by high-resolution 31P-nuclear magnetic resonance (NMR) spectroscopy and matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS). The most important result of this study is that the PL compositions of SF and serum of horse and dog are comparable with those of human body fluids. Compared with humans, however, the horse body fluid contains less PCs with highly unsaturated arachidonoyl residues, while that of dogs possesses the highest content of arachidonoyl-containing PC. These species-related differences stem primarily from different nutrition habits (meat vs. plants).
19753185 Mitchell's osteotomy in the management of hallux valgus: An Indian perspective. 2009 Jan BACKGROUND: Hallux valgus is a common condition that affects the forefoot. A large number of procedures are described for managing this condition. Mitchell's osteotomy and its modifications are being widely used for treating hallux valgus. However, most of the studies describe the results from the developed world. We present results of the classic Mitchell's osteotomy in hallux valgus in Indian subcontinent. MATERIALS AND METHODS: Forty eight adult patients (including 12 bilateral ones) in the age range of 18-60 years with hallux valgus were managed with the classic Mitchell's osteotomy. Pain over the bunion was the reason for surgery in 53 of 60 feet and cosmesis in the remaining 7 feet. Patients with hallux valgus angle more than 20 degrees and not responding to a trial of conservative treatment were included. Patients having metatarsophalangeal (MTP) joint osteoarthritis (Grade II and higher), hallux rigidus, rheumatoid arthritis, and with subluxation of MTP joint were excluded from the study. Further, patients with first metatarsal more than 3 mm shorter than second metatarsal were also excluded. RESULTS: The average follow-up period is 3 yrs (range 18months - 6yrs). About 55 feet (83%) were painless after surgery. Forty-two (70%) patients were happy with the cosmetic results of the surgery. Metatarsalgia was the reason for dissatisfaction with the procedure in five patients. The average correction of hallux valgus and the intermetatarsal angles achieved was 19.7 degrees and 6.9 degrees , respectively. Using the Broughton and Winson scoring system, 37 (61.7%) feet had excellent results, 18 (30%) had good, and five (8.3%) feet had a poor results. CONCLUSION: The classic Mitchell's procedure is a simple procedure and gives good cosmetic and radiological results.
19428330 Mechanisms of interferon-beta effects on bone homeostasis. 2009 Jun 15 Restoration of dysregulated bone homeostasis is a therapeutic goal in many diseases including osteoporosis, rheumatoid arthritis and metastatic cancer. The molecular pathways regulating bone remodeling are major therapeutic targets, and studies continue to reveal endogenous factors that may be pathologically up- or down-regulated and lead to an uncoupling of bone formation and resorption. The purpose of this commentary is to highlight new mechanisms of bone homeostatic regulation mediated through the induction of endogenous interferon-beta (IFN-beta). The receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) is an important factor in the bone resorption cascade, and the RANK-RANKL interaction has been shown to induce IFN-beta and osteoclastogenesis via induction of the c-fos gene. Subsequent binding of IFN-beta to its biological receptor initiates a signal transduction cascade through the classic JAK/STAT pathway, causing an inhibition of c-fos protein production and osteoclast proliferation and differentiation (negative feedback). Another mechanism pertinent to the anti-resorptive effect of IFN-beta is the induction of nitric oxide which has been shown to inhibit osteoclast formation. The role of IFN-beta in bone metabolism could warrant its systematic evaluation as a potential adjunct to therapeutic regimens of osteolytic diseases. Here we also provide discussion of the potential challenges to optimizing IFN-beta pharmacotherapy for such purposes.
19183043 Novel pyrrolidine ureas as C-C chemokine receptor 1 (CCR1) antagonists. 2009 Mar 12 Monocyte infiltration is implicated in a variety of diseases including multiple myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1 (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage inflammatory protein 1alpha (MIP-1alpha) and regulated on normal T-cell expressed and secreted (RANTES), mediates monocyte trafficking to sites of inflammation. High throughput screening of our combinatorial collection identified a novel, moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of monocytes with an IC(50) of 20 nM. In addition, the compound was highly selective over other chemokine receptors. It had good microsomal stability when incubated with rat and human liver microsomes and showed no significant cytochrome P450 (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed good oral bioavailability.
22461093 Pharmacogenetics: implementing personalized medicine. 2009 Jan Pharmacogenetics and pharmacogenomics have been widely recognized as fundamental steps toward personalized medicine. They deal with genetically determined variants in how individuals respond to drugs, and hold the promise to revolutionize drug therapy by tailoring it according to individual genotypes.The clinical need for novel approaches to improve drug therapy derives from the high rate of adverse reactions to drugs and their lack of efficacy in many individuals that may be predicted by pharmacogenetic testing.Significant advances in pharmacogenetic research have been made since inherited differences in response to drugs such as isoniazid and succinylcholine were explored in the 1950s. The clinical utility and applications of pharmacogenetics and pharmacogenomics are at present particularly evident in some therapeutic areas (anticancer, psycotrophic, and anticoagulant drugs).Recent evidence derived from several studies includes screening for thiopurine methyl transferase or uridine 5'-diphosphoglucuronosyl-transferase 1A1 gene polymorphisms to prevent mercaptopurine and azathioprine or irinotecan induced myelosuppression, respectively. Also there is a large body of information concerning cytochrome P450 gene polymorphisms and their relationship to drug toxicity and response. Further examples include screening the presence of the HLA-B*5701 allele to prevent the hypersensitivity reactions to abacavir and the assessment of the human epidermal growth factor receptor (HER-2) expression for trastuzumab therapy of breast cancer or that of KRAS mutation status for cetuximab or panitumumab therapy in colorectal cancer.Moreover, the application of pharmacogenetics and pharmacogenomics to therapies used in the treatment of osteoarticular diseases (e.g. rheumatoid arthritis, osteoporosis) holds great promise for tailoring therapy with clinically relevant drugs (e.g. disease-modifying antirheumatic drugs, vitamin D, and estrogens). Although the classical candidate gene approach has helped unravel genetic variants that influence clinical drug responsiveness, gene-wide association studies have recently gained attention as they enable to associate specific genetic variants or quantitative differences in gene expression with drug response.Although research findings are accumulating, most of the potential of pharmacogenetics and pharmacogenomics remains to be explored and must be validated in prospective randomized clinical trials.The genetic and molecular foundations of personalized medicine appear solid and evidence indicates its growing importance in healthcare.
20484466 Glucocorticoid receptor-beta and receptor-gamma exert dominant negative effect on gene rep 2010 Jul Glucocorticoid has diverse biological effects through induction or repression of its target genes via glucocorticoid receptor (GR). In addition to the wild-type GR (GR-alpha), a variety of GR variants has been reported, and these are thought to modify glucocorticoid action. Among others, GR-beta is reported be responsible for the glucocorticoid resistance frequently observed in steroid-resistant nephrotic syndrome, rheumatoid arthritis, and hematologic tumors, although the precise molecular mechanism remains unclear. In this study, we examined the function of GR-beta and some GR variants (GR-gamma and GR-Delta313-338) using GR-deficient BE(2)C and T84 cells in vitro. We found that GR-beta, when expressed alone, completely lost the capacity of both trans-activation and trans-repression on GR target genes. Interestingly, however, GR-beta showed a dominant-negative effect on GR-alpha only for its trans-repressive effects on cAMP-mediated and cAMP response element-dependent genes. Furthermore, both GR-beta and GR-gamma had dominant-negative effects on GR-alpha selectively for its trans-repressive effects on nuclear factor-kappaB-mediated and inflammation-related genes. These results suggest that 1) the GR-beta variant by itself has no receptor function, but 2) GR-beta and GR-gamma have properties to exert dominant-negative effects on the GR-alpha-mediated trans-repression, which may be responsible for the steroid resistance frequently observed in chronic inflammatory diseases under glucocorticoid therapy.
20346963 Hypothalamic mechanisms in cachexia. 2010 Jul 14 The role of nutrition and balanced metabolism in normal growth, development, and health maintenance is well known. Patients affected with either acute or chronic diseases often show disorders of nutrient balance. In some cases, a devastating state of malnutrition known as cachexia arises, brought about by a synergistic combination of a dramatic decrease in appetite and an increase in metabolism of fat and lean body mass. Other common features that are not required for the diagnosis include decreases in voluntary movement, insulin resistance, and anhedonia. This combination is found in a number of disorders including cancer, cystic fibrosis, AIDS, rheumatoid arthritis, renal failure, and Alzheimer's disease. The severity of cachexia in these illnesses is often the primary determining factor in both quality of life, and in eventual mortality. Indeed, body mass retention in AIDS patients has a stronger association with survival than any other current measure of the disease. This has led to intense investigation of cachexia and the proposal of numerous hypotheses regarding its etiology. Most authors suggest that cytokines released during inflammation and malignancy act on the central nervous system to alter the release and function of a number of neurotransmitters, thereby altering both appetite and metabolic rate. This review will discuss the salient features of cachexia in human diseases, and review the mechanisms whereby inflammation alters the function of key brain regions to produce stereotypical illness behavior. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.
20122230 An automated framework for understanding structural variations in the binding grooves of M 2010 Jan 18 BACKGROUND: MHC/HLA class II molecules are important components of the immune system and play a critical role in processes such as phagocytosis. Understanding peptide recognition properties of the hundreds of MHC class II alleles is essential to appreciate determinants of antigenicity and ultimately to predict epitopes. While there are several methods for epitope prediction, each differing in their success rates, there are no reports so far in the literature to systematically characterize the binding sites at the structural level and infer recognition profiles from them. RESULTS: Here we report a new approach to compare the binding sites of MHC class II molecules using their three dimensional structures. We use a specifically tuned version of our recent algorithm, PocketMatch. We show that our methodology is useful for classification of MHC class II molecules based on similarities or differences among their binding sites. A new module has been used to define binding sites in MHC molecules. Comparison of binding sites of 103 MHC molecules, both at the whole groove and individual sub-pocket levels has been carried out, and their clustering patterns analyzed. While clusters largely agree with serotypic classification, deviations from it and several new insights are obtained from our study. We also present how differences in sub-pockets of molecules associated with a pair of autoimmune diseases, narcolepsy and rheumatoid arthritis, were captured by PocketMatch13. CONCLUSION: The systematic framework for understanding structural variations in MHC class II molecules enables large scale comparison of binding grooves and sub-pockets, which is likely to have direct implications towards predicting epitopes and understanding peptide binding preferences.
20190313 Long-term follow-up of replacement compared with internal fixation for displaced femoral n 2010 Mar In a series of 450 patients over 70 years of age with displaced fractures of the femoral neck sustained between 1995 and 1997 treatment was randomised either to internal fixation or replacement. Depending on age and level of activity the latter was either a total hip replacement or a hemiarthroplasty. Patients who were confused or bed-ridden were excluded, as were those with rheumatoid arthritis. At ten years there were 99 failures (45.6%) after internal fixation compared with 17 (8.8%) after replacement. The rate of mortality was high at 75% at ten years, and was the same in both groups at all times. Patient-reported pain and function were similar in both groups at five and ten years. Those with successfully healed fractures had more hip pain and reduction of mobility at four months compared with patients with an uncomplicated replacement, and they never attained a better outcome than the latter patients regarding pain or function. Primary replacement gave reliable long-term results in patients with a displaced fracture of the femoral neck.
20170006 [Helicobacter pylori infection and autoimmune disease such as immune thrombocytopenic purp 2010 Jan Helicobacter pylori infection is implicated in the pathogenesis of extradigestive diseases such as acne rosacea and idiopathic chronic urticaria and autoimmune diseases such as autoimmune gastric atrophy, rheumatoid arthritis, anti phospholipid antibody syndrome, autoimmune thyroiditis, Sjoegren syndrome, Henoch-Schoenlein purpura, and Type B insulin resistance syndrome. H. pylori eradication ameliorated the condition in some, but not all, of those with these autoimmune diseases. Recent studies primarily in Italy and Japan found that H. pylori eradication in those infected with chronic immune thrombocytopenic purpura (ITP) results in a persistent platelet count increase in over half of those treated, suggesting that although pathogenetic mechanisms underlying the relationship between H. pylori infection and autoimmune disease remain unclear, yet-unknown immunological events induced by H. pylori infection almost certainly occur in the development of autoimmune response. A majority of isolated H. pylori strains express human Lewis (Le(x) and/or Le(y) determinants and in some strains, Le(a), Le(b), sialyl-Le(x)), and H determinants in the O-chain of the surface lipopolysaccharide. Previous studies showed that this molecular mimicry helps the bacterium evade host responses while evoking autoantibody responses to Le antigens. The anti-Le(y) autoantibody is also reported to promote H. pylori adhesion to gastric epithelial cells, leading to development of gastric atrophy. Moreover, one can hypothesize that anti-Le autoreactive antibodies induced by H. pylori infection are involved in the development of autoimmune diseases, although no clinical studies showing that anti-Le immune responses are involved in the etiology of these autoimmune diseases have been conducted. Proving this hypothesis would require quantitative and qualitative analysis of autoantibodies and T cell functions to Le antigens. High frequent phase variation of Le structures in the O-polysaccharide of H. pylori may influence the immune response of patients to Le antigens.
20156947 Visual assessment of the spine bruckel instrument, a novel status tool to reflect appearan 2010 Mar OBJECTIVE: The Visual Assessment of the Spine Bruckel Instrument (VASBI) is a new status tool developed by the Spondylitis Association of America and the University of Toronto to reflect spinal appearance in patients with ankylosing spondylitis (AS). Our objective was to validate the VASBI according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials filter (truth, discrimination, and feasibility). METHODS: Three hundred patients with AS were asked to rate their degree of perceived spinal deformity using the VASBI. To evaluate construct validity, VASBI scores were compared with functional outcome, spinal mobility, and radiographic spinal damage. Test-retest reliability was evaluated using kappa statistic (kappa). RESULTS: Patient VASBI demonstrated strong correlation with spinal mobility (r = 0.543) and moderate correlation with functional impairment (r = 0.490) and structural damage (r = 0.309). Reliability for VASBI was very good (kappa = 0.973, p < 0.001). CONCLUSION: The VASBI is a novel tool with practical applications in a busy clinical setting as it simplifies assessment of AS spinal deformity. Our study demonstrates that the VASBI has good feasibility, construct validity, and reliability.
20036578 Subsequent autoimmune or related disease in asthma patients: clustering of diseases or med 2010 Mar PURPOSE: Asthma includes immunological components that may share mechanisms with autoimmune diseases. We analyzed the subsequent occurrence of any of 22 autoimmune and related conditions in hospitalized asthma patients. METHODS: A nationwide study was conducted in Sweden on subsequent diseases of asthma patients on the basis of the Hospital Discharge Register. Standardized incidence ratios (SIRs) were calculated for subsequent autoimmune diseases. RESULTS: A total of 4006 patients were hospitalized for an autoimmune condition after last hospitalization for asthma. The SIRs were increased for 11 subsequent autoimmune conditions, diagnosed at least 5 years after asthma. The highest SIRs were noted for polyarteritis nodosa (4.29) and Addison disease (3.62). SIRs for these diseases and others, including the most common autoimmune disease rheumatoid arthritis, were increased even when the follow-up was started 5 years after the last asthma hospitalization. Addison disease and Crohn disease were increased in asthma patients hospitalized at various ages, whereas young asthma patients presented with celiac disease and immune thrombocytopenic purpura. CONCLUSIONS: Hospitalized asthma patients presented with a number of subsequent autoimmune and related diseases. Although we were unable to exclude the effects of environmental factors, the data suggest that shared genetic factors or gene-environment interactions may explain coexistence of some of these diseases.
20018077 Incorporating biological knowledge in the search for gene x gene interaction in genome-wid 2009 Dec 15 We sought to find significant gene x gene interaction in a genome-wide association analysis of rheumatoid arthritis (RA) by performing pair-wise tests of interaction among collections of single-nucleotide polymorphisms (SNPs) obtained by one of two methods. The first method involved screening the results of the genome-wide association analysis for main effects p-values < 1 x 10-4. The second method used biological databases such as the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes to define gene collections that each contained one of four genes with known associations with RA: PTPN22, STAT4, TRAF1, and C5. We used a permutation approach to determine whether any of these SNP sets had empirical enrichment of significant interaction effects. We found that the SNP set obtained by the first method was significantly enriched with significant interaction effects (empirical p = 0.003). Additionally, we found that the "protein complex assembly" collection of genes from the Gene Ontology collection containing the TRAF1 gene was significantly enriched with interaction effects with p-values < 1 x 10-8 (empirical p = 0.012).
20018056 Combining least absolute shrinkage and selection operator (LASSO) and principal-components 2009 Dec 15 Variable selection in genome-wide association studies can be a daunting task and statistically challenging because there are more variables than subjects. We propose an approach that uses principal-component analysis (PCA) and least absolute shrinkage and selection operator (LASSO) to identify gene-gene interaction in genome-wide association studies. A PCA was used to first reduce the dimension of the single-nucleotide polymorphisms (SNPs) within each gene. The interaction of the gene PCA scores were placed into LASSO to determine whether any gene-gene signals exist. We have extended the PCA-LASSO approach using the bootstrap to estimate the standard errors and confidence intervals of the LASSO coefficient estimates. This method was compared to placing the raw SNP values into the LASSO and the logistic model with individual gene-gene interaction. We demonstrated these methods with the Genetic Analysis Workshop 16 rheumatoid arthritis genome-wide association study data and our results identified a few gene-gene signals. Based on our results, the PCA-LASSO method shows promise in identifying gene-gene interactions, and, at this time we suggest using it with other conventional approaches, such as generalized linear models, to narrow down genetic signals.
20018042 Assessment of genotype imputation methods. 2009 Dec 15 Several methods have been proposed to impute genotypes at untyped markers using observed genotypes and genetic data from a reference panel. We used the Genetic Analysis Workshop 16 rheumatoid arthritis case-control dataset to compare the performance of four of these imputation methods: IMPUTE, MACH, PLINK, and fastPHASE. We compared the methods' imputation error rates and performance of association tests using the imputed data, in the context of imputing completely untyped markers as well as imputing missing genotypes to combine two datasets genotyped at different sets of markers. As expected, all methods performed better for single-nucleotide polymorphisms (SNPs) in high linkage disequilibrium with genotyped SNPs. However, MACH and IMPUTE generated lower imputation error rates than fastPHASE and PLINK. Association tests based on allele "dosage" from MACH and tests based on the posterior probabilities from IMPUTE provided results closest to those based on complete data. However, in both situations, none of the imputation-based tests provide the same level of evidence of association as the complete data at SNPs strongly associated with disease.
19922529 Epidemiology and comorbidity of psoriasis in children. 2010 Mar BACKGROUND: Psoriasis is a common disease affecting all age groups. In contrast to adult psoriasis, only few studies on the epidemiology of childhood psoriasis have been published. OBJECTIVES: Assessment of prevalence and comorbidities of juvenile psoriasis in Germany based on health insurance data. METHODS: Data were collected from a database of about 1.3 million nonselected individuals from a German statutory health insurance organization which covers all geographical regions. Individuals with psoriasis were identified by ICD-10 codes applied to all outpatient and inpatient visits. The present analysis consists of all patients who were enlisted throughout the year 2005. The diagnosis of psoriasis was registered whenever there was at least one documented patient contact using code L40.* and subcodes. Comorbidities were also evaluated by ICD-10 diagnoses. RESULTS: In total, 33 981 patients with the diagnosis of psoriasis were identified. The prevalence in 2005 was 2.5%. The total rate of psoriasis in children younger than 18 years was 0.71%. The prevalence rates increased in an approximately linear manner from 0.12% at the age of 1 year to 1.2% at the age of 18 years. The overall rate of comorbidity in subjects with psoriasis aged under 20 years was twice as high as in subjects without psoriasis. Juvenile psoriasis was associated with increased rates of hyperlipidaemia, obesity, hypertension, diabetes mellitus, rheumatoid arthritis and Crohn disease. CONCLUSIONS: Psoriasis is a common disease in children. Like in adults, it is associated with significant comorbidity. Increased attention should be paid to the early detection and treatment of patients affected.