SEARCH · PubMed Health

Results for “shared variables”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources

PubMed2003

Portuguese families with dentatorubropallidoluysian atrophy (DRPLA) share a common haplotype of Asian origin.

Dentatorubropallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by a variable combination of progressive ataxia, epilepsy, myoclonus, choreoathetosis and dementia. This disease is caused by a (CAG)(n) expansion in the DRPLA gene, on chromosome 12p13. DRPLA is prevalent in Japan, but several families of non-Japanese ancestry have already been published. To identify the origin of expanded alleles in Portuguese families with DRPLA, we studied two previously reported intragenic SNPs in introns 1 and 3, in addition to the CAG repeat of the DRPLA gene. The results showed that all four Portuguese DRPLA families shared the same haplotype, which is also common to that reported for Japanese DRPLA chromosomes. This haplotype is also the most frequent in Japanese normal alleles, whereas it was rare in Portuguese control chromosomes. Thus, our findings support that a founder DRPLA haplotype of Asian origin was introduced in Portugal, being responsible for the frequency of the disease in this country.

Alleles↗

PubMed1993

A hypothesis for the HLA-B27 immune dysregulation in spondyloarthropathy: contributions from enteric organisms, B27 structure, peptides bound by B27, and convergent evolution.

Several human rheumatic diseases occur predominantly in persons who carry the histocompatibility (HLA) class I allele B27. They have also been related to Gram-negative enteric microorganisms. In addition, the recent recovery of peptides bound to B27 has allowed an understanding of the structural requirements for their binding. Using the accumulated data base of protein sequences, we have tested a series of hypotheses. First, we have asked whether the primary amino acid sequence of the hypervariable regions of HLA-B27 shares short sequences with the proteins of Gram-negative enteric bacteria. The data demonstrate that, unique among the HLA-B molecules, the hypervariable regions of HLA-B27 unexpectedly share short peptide sequences with proteins from these bacteria. Second, we have asked whether the enteric proteins tend to satisfy the structural requirements for peptide binding to B27 in those regions of the sequence shared with B27. This hypothesis also tends to be true, especially in an allelically variable part of the B27 sequence which is predicted to bind B27 if it were to be presented as a free peptide. We conclude that HLA-B27 and enteric Gram-negative bacteria have undergone a previously unappreciated form of convergent evolution which may be important in the process leading to these rheumatic diseases. Moreover, the regions of the enteric bacterial proteins which are contiguous with the short sequences shared with B27 tend to have structures which are also predicted to bind B27. These observations suggest a mechanism for autoimmunity and lead to the prediction that the B27-associated diseases are mediated by a subset of T-cell receptors, B27, and the peptides bound by B27.

Amino Acid Sequence↗

PubMed1994

Pathophysiology of sodium channelopathies: correlation of normal/mutant mRNA ratios with clinical phenotype in dominantly inherited periodic paralysis.

It is often suggested that polygenic or environmental factors are responsible for clinical variability between patients with identical mutations. However, most dominant diseases are caused by a change-of-function alteration in the mutant allele's protein product. All patients are heterozygous and presumably express both mutant and normal proteins from the corresponding genes. Thus, a possible molecular mechanism for clinical variability could be the difference in relative levels of mutant vs. normal mRNA in different patients with the same mutation. To investigate this hypothesis, it is necessary to have access to a series of tissue biopsies from many patients with the same mutation causing a clinically variable dominant disease. Human hyperkalemic periodic paralysis (HyperPP) has been shown to be a clinically variable disorder caused by change-of-function mutations of the skeletal muscle sodium channel protein. We recently identified a large (> 50,000) pedigree of affected Quarter Horses sharing the same causative amino acid alteration of the muscle sodium channel protein. The horses like humans show substantial clinical variability. In this report, we developed a fluorescent reverse transcription-polymerase chain reaction assay which quantifies the relative levels of normal and mutant mRNA expression of the horse adult skeletal muscle sodium channel gene in affected Quarter Horses. We found that asymptomatic horses showed more normal sodium channel mRNA, while moderately affected horses showed more mutant mRNA. The ratios of mutant/normal mRNA between these two groups are statistically different, suggesting that severity of HyperPP Quarter Horses may indeed be correlated to the ratio of mutant and normal sodium channel gene expression in skeletal muscle.

Animals↗

PubMed2007

Impact of marriage on HIV/AIDS risk behaviors among impoverished, at-risk couples: a multilevel latent variable approach.

Studies among normative samples generally demonstrate a positive impact of marriage on health behaviors and other related attitudes. In this study, we examine the impact of marriage on HIV/AIDS risk behaviors and attitudes among impoverished, highly stressed, homeless couples, many with severe substance abuse problems. A multilevel analysis of 368 high-risk sexually intimate married and unmarried heterosexual couples assessed individual and couple-level effects on social support, substance use problems, HIV/AIDS knowledge, perceived HIV/AIDS risk, needle-sharing, condom use, multiple sex partners, and HIV/AIDS testing. More variance was explained in the protective and risk variables by couple-level latent variable predictors than by individual latent variable predictors, although some gender effects were found (e.g., more alcohol problems among men). The couple-level variable of marriage predicted lower perceived risk, less deviant social support, and fewer sex partners but predicted more needle-sharing.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Distinctive repertoire of contingency genes conferring mutation- based phase variation and combinatorial expression of surface lipoproteins in Mycoplasma capricolum subsp. capricolum of the Mycoplasma mycoides phylogenetic cluster.

The generation of surface variation among many divergent species of Mollicutes (mycoplasmas) occurs through stochastic expression patterns of diverse lipoprotein genes. The size and wide distribution of such variable gene sets in minimal (approximately 0.6- to 1.4-Mb) mycoplasmal genomes suggest their key role in the adaptation and survival of these wall-less monoderms. Diversity through variable genes is less clearly established among phylogenetically similar mycoplasmas, such as the Mycoplasma mycoides cluster of ruminant pathogens, which vary widely in host range and pathobiology. Using (i) genome sequences from two members of this clade, Mycoplasma capricolum subsp. capricolum and M. mycoides subsp. mycoides small colony biotype (SC), (ii) antibodies to specific peptide determinants of predicted M. capricolum subsp. capricolum gene products, and (iii) analysis of the membrane-associated proteome of M. capricolum subsp. capricolum, a novel set of six genes (vmcA to vmcF) expressing distinct Vmc (variable M. capricolum subsp. capricolum) lipoproteins is demonstrated. These occur at two separate loci in the M. capricolum subsp. capricolum genome, which shares striking overall similarity and gene synteny with the M. mycoides subsp. mycoides SC genome. Collectively, Vmc expression is noncoordinate and combinatorial, subject to a single-unit insertion/deletion in a 5' flanking dinucleotide repeat that governs expression of each vmc gene. All vmc genes share modular regions affecting expression and membrane translocation. In contrast, vmcA to vmcD genes at one locus express surface proteins with highly structured size-variable repeating domains, whereas vmcE to vmcF genes express products with short repeats devoid of predicted structure. These genes confer a distinctive, dynamic surface architecture that may represent adaptive differences within this important group of pathogens as well as exploitable diagnostic targets.

5' Flanking Region↗

PubMed1995

A comparison of the determinants of safe injecting and condom use among injecting drug users.

A sample of 582 injecting drug users were interviewed as part of an evaluation of an AIDS prevention programme for drug users. This paper examines the biographic and predispositional determinants of five HIV preventive behaviours--equipment sharing (not receiving and not giving) and and condom use (with regular partners, casual partners and sex clients). A two-stage sequential approach was adopted for a logistic regression analysis. Initially, to model each of the five preventive behaviours, biographical and drug use variables were entered. In a second set of models, behavioural predisposition factors were included. Age, drug use and prison experience correlate with variables in both models, although not consistently in the same direction. While a predisposition to reject sharing correlates with safer rejecting and condom use, the predisposition to safer sex only correlates with condom use. Needle exchange programmes that only target the individual would seem to be inadequate. To enhance targeted interventions changes in public and agency policy that create a social environment conductive to behaviour change are required.

Acquired Immunodeficiency Syndrome↗

PubMed1976

Idiotypic analysis of lymphocytes in vitro. I. Specificity and heterogeneity of B and T lymphocytes reactive with anti-idiotypic antibody.

Guinea pig anti-idiotypic antibodies (anti-Id) of the IgG1 class, directed to an A/J antibody to Group A streptococcal carbohydrate (A-CHO), or directed to a BALB/c myeloma protein that binds the same antigen, stimulate B-precursor cells as well as T-helper cells when injected into mice of the appropriate strain. The strain-specific induction of both precursor and helper activity was detected by in vitro secondary responses of primed spleen cells to A-CHO or to 2,4,6-trinitrophenyl (TNP) upon challenge with Group A streptococcal vaccine (Strep.A) or with TNP-Strep.A, respectively. B- and T-cell populations primed with anti-Id were uniform with respect to the binding of antigen and of anti-Id. This was in contrast to cells primed with Strep.A, which were heterogenous. Taken together, B and T cells that possess the same antigen-binding specificity share idiotypic determinants, reveal the same idiotypic polymorphism, and may display similar degrees of heterogeneity with respect to the binding of antigen and anti-Id. Since the anti-Id used in this study detect Id determinants associated with the heavy chain of the variable region of mouse antibodies, the data suggest that this region of the immunoglobulin molecule is shared between T- and B-cell antigen receptors.

Acetylglucosamine↗

PubMed2026

Complete genome of multiply antibiotic resistant ST10 Acinetobacter baumannii isolate NL6 from Vietnam and relationship to available ST10 genomes.

The genome of NL6, a multiply antibiotic-resistant Acinetobacter baumannii ST10:KL49:OCL2 carriage isolate from Vietnam, was sequenced using Nanopore technology, and complete chromosome and plasmid sequences were assembled from the long reads and available short reads. Resistance genes and their locations were identified, and transfer of a conjugative plasmid carrying several resistance genes into a new host was tested. The acquired resistance genes in NL6 were distributed between the chromosome and two of three plasmids present. The chromosome carries multiple copies of several insertion sequences, an incomplete copy of the ISAba1-bounded Tn6250 that includes the sul2 and strAB genes, and an integrative element carrying copper resistance genes designated IECuR. Plasmid pNL6-2 (r3-T5; 15 Kbp) is a Rep_3/OrfX plasmid that includes a tet39 dif module, and pNL6-3 (r3-T20; 66.9 Kbp) carries aacC2d, aphA6, and blaCARB-16 and a second ampC gene preceded by an ISAba1. Conjugation of pNL6-3 into derivatives of ATCC17978 was demonstrated, confirming that the ampC gene confers resistance to third-generation cephalosporins. NL6 was compared to other complete ST10 genomes. Several acquired elements in the chromosome were shared with the ST10 isolate LAC-4 (USA), indicating shared ancestry, but the plasmid content differed. The KL and plasmid content were variable in 17 further complete ST10 genomes downloaded from GenBank. Tn6250 and IECuR were only found together in the chromosome of two further KL49 isolates. Antibiotic resistance in ST10 A. baumannii was acquired mainly via plasmid acquisition, but resistance genes varied, and a variety of plasmids was involved.IMPORTANCEMembers of the CC10 clonal complex of Acinetobacter baumannii comprising ST10 plus single and double locus variants are known to be particularly virulent. However, antibiotic resistance in members of this group has rarely been examined. Here, determination of the complete genome (chromosome and plasmids) of a representative ST10 isolate from Vietnam allowed the context and location of acquired antibiotic resistance genes and of other mobile genetic elements to be determined. Mobile genetic element locations in completed chromosomes facilitate comparisons of potentially related genomes, revealing those with recent shared ancestry. Differences in plasmid content can also be examined.

Acinetobacter baumannii↗

PubMed2003

Prediction of 3-yr cadaveric graft survival based on pre-transplant variables in a large national dataset.

Pre- and post-transplant predictive factors of graft survival for optimal and expanded criteria grafts have been studied in the past. The goal of our study was to evaluate the recent large set of United Network of Organ Sharing records (1990-1998) to generate a prediction algorithm of 3-yr graft survival based on pre-transplant variables alone. The dataset of patients with end-stage renal disease and cadaveric kidney or kidney-pancreas transplantation (1990-1998) used in the study consisted of 37,407 records. Logistic regression (LM) and a tree-based model (TBM) were used to identify predictors of 3-yr allograft survival and to generate prediction algorithm. Donor and recipient demographic characteristics (age, race, and gender) and body mass index showed non-linear, while human leukocyte antigen match showed strong linear relationships with 3-yr graft survival. Prediction of the probability of graft survival from the model, achieved a good match with the observed survival of the separate dataset, with a correlation of r = 0.998 for LM and r = 0.984 for TBM. The positive predictive value (PV) of allograft survival with LM and TBM was 76.0% and the negative PV was 63 and 53.8% for LM and TBM, respectively. Both LM and the TBM can potentially be used in clinical practice for long-term prediction of kidney allograft survival based on pre-transplant variables.

Algorithms↗

PubMed1988

Spatial clumping of sexually receptive females induces space sharing among male voles.

The spatial organization of individuals in populations (their spacing system) can be highly variable even among populations of the same species. As spacing systems have important consequences for ecological processes such as population regulation, competition and mating systems, there have been many attempts to explore factors that may cause this variation. For mammals, it has been argued that the spatial distribution of sexually receptive females is the most important factor determining the spacing system of males, whereas habitat characteristics are most important to females. This has been difficult to test experimentally as it requires manipulations of the spatial distribution of the opposite sex without changing other properties of the environment. Here, I present a novel experimental procedure that can achieve this and demonstrate that the spatial distribution of the opposite sex in a population of voles is indeed an important determinant of the spacing system of males, but not of females. However, the effects on males are different from those predicted by many theoretical studies.

Animals↗

PubMed1994

A human rheumatoid factor C304 shares VH and VL gene usage with antibodies specific for ubiquitous human viral pathogens.

Analysis of the variable region gene sequences of a human hybridoma rheumatoid factor (RF), derived from a patient with rheumatoid arthritis (RA), revealed the expression of genes from the V lambda I and VH3 families. Specifically, the C304 RF had rearranged the DPL8/Humlv1042 and VH26 germline VL and VH genes, respectively. This gene usage has been observed in the rearrangement of human anti-viral antibodies specific for the herpes group of viruses. This overlap between the autoimmune and anti-viral antibody gene repertoires suggests a possible structural relationship between the immune response directed against ubiquitous pathogens and the induction of RF production.

Amino Acid Sequence↗

PubMed2006

Molecular characterization of deletion breakpoints in adults with 22q11 deletion syndrome.

22q11 Deletion syndrome (22q11DS) is a common microdeletion syndrome with variable expression, including congenital and later onset conditions such as schizophrenia. Most studies indicate that expression does not appear to be related to length of the deletion but there is limited information on the endpoints of even the common deletion breakpoint regions in adults. We used a real-time quantitative PCR (qPCR) approach to fine map 22q11.2 deletions in 44 adults with 22q11DS, 22 with schizophrenia (SZ; 12 M, 10 F; mean age 35.7 SD 8.0 years) and 22 with no history of psychosis (NP; 8 M, 14 F; mean age 27.1 SD 8.6 years). QPCR data were consistent with clinical FISH results using the TUPLE1 or N25 probes. Two subjects (one SZ, one NP) negative for clinical FISH had atypical 22q11.2 deletions confirmed by FISH using the RP11-138C22 probe. Most (n = 34; 18 SZ, 16 NP) subjects shared a common 3 Mb hemizygous 22q11.2 deletion. However, eight subjects showed breakpoint variability: a more telomeric proximal breakpoint (n = 2), or more centromeric (n = 3) or more telomeric distal breakpoint (n = 3). One NP subject had a proximal nested 1.4 Mb deletion. COMT and TBX1 were deleted in all 44 subjects, and PRODH in 40 subjects (19 SZ, 21 NP). The results delineate proximal and distal breakpoint variants in 22q11DS. Neither deletion extent nor PRODH haploinsufficiency appeared to explain the clinical expression of schizophrenia in the present study. Further studies are needed to elucidate the molecular basis of schizophrenia and clinical heterogeneity in 22q11DS.

Adult↗

PubMed2004

A simulation study concerning the effect of varying the residual phenotypic correlation on the power of bivariate quantitative trait loci linkage analysis.

The power of bivariate variance components (VC) linkage analysis is affected by the size and source of the phenotypic correlation between variables. In particular, several authors have suggested that the power to detect linkage is greatest when the quantitative trait locus (QTL) and residual sources of variation induce phenotypic covariation in opposite directions, and that this increase in power is greatest when unique environmental sources of variation induce covariation in the direction opposite to the QTL. The purpose of the present study was to investigate further the effect of varying the residual correlation between variables on the power to detect linkage in a bivariate variance components linkage analysis. Data were simulated for a biallelic QTL that pleiotropically influenced two variables. The power to detect linkage was calculated under a variety of situations in which the proportion of phenotypic covariance resulting from shared sources of variation and from unique sources of variation was varied. These simulations were performed for the case in which the QTL affected the two variables equally and also for the case in which the QTL made unequal contributions to each variable. Our results confirm that the power to detect QTLs in a bivariate test for linkage depends upon the size and source of the residual correlation between variables, being greatest when the QTL and unique environmental sources of variation induce phenotypic covariation in opposite directions. We also found that when the QTL affected the two variables unequally, the power to detect linkage increased markedly as the correlation between unique environmental sources of variation increased from 0.6 to 0.9. Similar results were obtained under a variety of genetic models, including when there were unequal allele frequencies and dominance at the QTL. We suggest that a promising strategy to increase the power to detect QTLs might be to collect data from variables where there is either good observational evidence (e.g., from multivariate structural equation modeling of twin data) or a sound theoretical argument that the QTL and environmental factors induce covariation in opposite directions.

Alleles↗

PubMed1979

Do natural killer cells engage in regulated reactions against self to ensure homeostasis?

Host reactivities not requiring immunization in the mouse, especially natural resistance of irradiated animals to accept grafts of normal or malignant hemopoietic cells, were compared with NK activity against the YAC-1 lymphoma. The effects of several independent variables known to influence natural resistance in vivo had a similar effect on the NK system. Figure 12 lists an impressive array of shared properties and positive correlations. In contrast, the distinctions were few and minor. Many of the positive correlations were of particular significance since the experimental variables either have opposing or no effects on conventional induced immunity. The multiplicity and pervasiveness of these correlations suggest that the cellular mechanisms underlying natural reactivities are similar or common. Cytotoxic effectors mediating natural resistance to normal cells, tumors, and cells infected with intracellular pathogens may be distinct in terms of target selectivity, yet belong to a single cell lineage subject to common regulatory influences for differentiation and function. Regulation of reactivity via suppressor cells was studied in the NK system only. The spleens of mice selected for low levels of NK activity (resulting from young age, irradiation, and treatment with the macrophage-active agents l-carrageenan or hydrocortisone acetate) contained cells capable of inhibiting the lytic function of NK effectors taken from untreated adult donors. All the suppressor cells studied were thymus-independent, as judged by their occurrence in spleens of genetically athymic mice; the suppressive function was resistant to 2000 rads of gamma-rays administered in vitro and was not restricted by the major histocompatibility complex, without exception. However, two major classes of suppressors were identified: (a) macrophagelike cells inducible by l-carrageenan or hydrocortisone acetate, and (b) nonadherent cells found in spleens of untreated infants and of irradiated adult mice. It is proposed that the suppression of NK cytolysis demonstrated in vitro was a manifestation of regulatory mechanisms modulating the level of NK activity in vivo. Macrophagelike cells that are induced, activated, or inactivated by bacteria, viruses, hormones, and other agents may act as regulators of differentiation, maturation, and function of cells belonging to the NK lineage. Nonadherent cells could be either a distinct class of suppressors or immature NK cells capable of binding but not lysing target cells. In the latter case, regulation would be achieved via competitive binding of targets by pre-NK cells presumably in dynamic equilibrium with functional (i.e. matured) NK effectors.

Animals↗

PubMed1986

The Boston Center for Liver Transplantation (BCLT). Initial experience of a new surgical consortium.

Improved survival following liver transplantation has led to a rapid increase in the number of centers providing this expensive and demanding therapy. In January 1984, four Boston hospitals launched a cooperative program known as the Boston Center for Liver Transplantation (BCLT). From January 1984 through July 1985, 47 liver transplantations were performed in 41 patients ranging in age from 8 months to 60 years. Donor organs were retrieved from 22 states within a 2,500-mile radius. Thirty-five of the 47 procedures were performed by teams consisting of surgeons from at least two BCLT member hospitals. Twelve-month actuarial survival was 54.1% without significant institutional variability. The BCLT has developed into a unique transplant consortium capable of sharing manpower, equipment, and organs without sacrificing quality of care of disrupting preexisting medical services.

Adolescent↗

PubMed2000

Extreme functional sensitivity to conservative amino acid changes on enzyme exteriors.

Mutagenesis studies and alignments of homologous sequences have demonstrated that protein function typically is compatible with a variety of amino-acid residues at most exterior non-active-site positions. These observations have led to the current view that functional constraints on sequence are minimal at these positions. Here, it is shown that this inference assumes that the set of acceptable residues at each position is independent of the overall sequence context. Two approaches are used to test this assumption. First, highly conservative replacements of exterior residues, none of which would cause significant functional disruption alone, are combined until roughly one in five have been changed. This is found to cause complete loss of function in vivo for two unrelated monomeric enzymes: barnase (a bacterial RNase) and TEM-1 beta-lactamase. Second, a set of hybrid sequences is constructed from the 50 %-identical TEM-1 and Proteus mirabilis beta-lactamases. These hybrids match the TEM-1 sequence except for a region at the C-terminal end, where they are random composites of the two parents. All of these hybrids are biologically inactive. In both experiments, complete loss of activity demonstrates the importance of sequence context in determining whether substitutions are functionally acceptable. Contrary to the prevalent view, then, enzyme function places severe constraints on residue identities at positions showing evolutionary variability, and at exterior non-active-site positions, in particular. Homologues sharing less than about two-thirds sequence identity should probably be viewed as distinct designs with their own sets of optimising features.

Amino Acid Sequence↗

PubMed2006

Channel catfish leukocyte immune-type receptors contain a putative MHC class I binding site.

The recent identification of a large and diverse family of leukocyte immune-type receptors (IpLITRs) in channel catfish (Ictalurus punctatus) indicates that immunoglobulin superfamily (IgSF) members related to both mammalian Fc receptors (FcRs) and leukocyte receptor complex (LRC)-encoded proteins exist in fish. In the present study, it was found that IpLITR messages were preferentially up regulated in catfish peripheral blood leukocytes (PBL) and clonal cytotoxic T cells (CTL) after alloantigen stimulation. Detailed sequence analyses of the expressed IpLITR cDNAs from two clonal CTL lines indicated an unexpectedly large array of putative activatory and inhibitory IpLITR-types containing variable numbers of extracellular immunoglobulin (Ig)-like domains. Importantly, all expressed IpLITRs shared similar membrane distal Ig domains (i.e., D1 and D2), suggesting that they may bind a common type of ligand. Sequence alignments and comparative homology modeling revealed that IpLITR domains, D1 and D2, have similar predicted 3-D structural properties with the corresponding domains of the human LRC-encoded leukocyte Ig-like receptor (LILR) family. Furthermore, conservation of key major histocompatibility class I (MHC I)-binding residues were located at similar positions within the membrane distal tip of D1 between representative IpLITRs and group 1 LILRs. Taken together, these results suggest that fish LITRs have an orthologous relationship to LRC-encoded receptors such as the human LILRs and could potentially function as a diverse family of MHC class I-binding receptors.

Amino Acid Sequence↗

PubMed2005

Clinical, laboratory and genetic markers associated with erosions and remission in patients with early inflammatory arthritis: a prospective cohort study.

We investigated the relationship between clinical, laboratory and genetic markers and outcome measures in 159 patients with recent onset of inflammatory arthritis (IA). The majority of patients were managed in community-based rheumatology practice. Median duration of arthritis at baseline was 3 months with median follow-up of 4.0 years (range 0-10). Markers of disease activity and 1987 ACR criteria for rheumatoid arthritis (RA) were estimated every 6 months for the first 2 years and annually thereafter. Presence of shared epitopes (SE) was established by PCR-based method. Main outcome variables were attainment of remission and presence of erosions on X-rays of hands and feet at 3 years. Remission was seen in 34.3% of patients and was independently related to age 60 and older (odds ratio (OR) 3.2; 95% confidence interval (CI), 1.2-8.7) and inversely to the presence of rheumatoid factor (RF) (OR 8.3; 95% CI, 3.2-21.3 for persistent arthritis). Patients with two SE were likely to have persistent arthritis (P=0.006), but this was not significant when corrected for RF. Independent predictors for erosions at 3 years were RF (OR 7.5; 95% CI, 1.9-29.5) and area under the curve for number of swollen joints (OR 1.08; 95% CI, 1.02-1.16). SE status was not predictive of erosions at 3 years (OR 1.6; 95% CI, 0.7-3.7). In univariate analysis, patients possessing DERAA motif on DRB1 were less likely to have erosive disease than without this motif at 4 years (OR 0.21; 95% CI, 0.0-0.9, P=0.037) but this finding was partly explained by adjusting for RF (adjusted OR 0.24; 95% CI 0.04-1.37). In this study of recent onset IA, active disease and RF were associated with poor outcome. Whilst SE did not predict erosive disease, patients with DERAA motif may be protected against erosions whilst the presence of two SE alleles suggests persistence of arthritis.

Age of Onset↗