Corrections: Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population (Annals of the Rheumatic Diseases (2011) 70, (1793-1797))

Patrick Danoy, Meng Wei, Hadler Johanna, et al. Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population. Ann Rheum Dis 2011;70:1793–97. The following authors were listed as contributing equally to the study...

An investigation of dose calculation accuracy in intensity-modulated radiotherapy of sites in the head & neck

Knowledge of the accuracy of dose calculations in intensity-modulated radiotherapy of the head and neck is essential for clinical confidence in these highly conformal treatments. High dose gradients are frequently placed very close to critical structures, such as the spinal cord, and good coverage of complex shaped nodal target volumes is important for long term-local control. A phantom study is presented comparing the performance of standard clinical pencil-beam and collapsed-cone dose algorithms to Monte Carlo calculation and three-dimensional gel dosimetry measurement. All calculations and measurements are normalized to the median dose in the primary planning target volume, making this a purely relative study. The phantom simulates tissue, air and bone for a typical neck section and is treated using an inverse-planned 5-field IMRT treatment, similar in character to clinically used class solutions. Results indicate that the pencil-beam algorithm fails to correctly model the relative dose distribution surrounding the air cavity, leading to an overestimate of the target coverage. The collapsed-cone and Monte Carlo results are very similar, indicating that the clinical collapsed-cone algorithm is perfectly sufficient for routine clinical use. The gel measurement shows generally good agreement with the collapsed-cone and Monte Carlo calculated dose, particularly in the spinal cord dose and nodal target coverage, thus giving greater confidence in the use of this class solution.

Corneal confocal microscopy : a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy

OBJECTIVE: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies. ---------- RESEARCH DESIGN AND METHODS: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM). ---------- RESULTS: Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = −0.475, P < 0.0001; NBD r = −0.511, P < 0.0001; and NFL r = −0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm2 with a sensitivity of 0.82 (95% CI 0.68–0.92) and specificity of 0.52 (0.40–0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm2 with a sensitivity of 0.71 (0.42–0.92) and specificity of 0.64 (0.54–0.74). ---------- CONCLUSIONS: CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity. Established diabetic neuropathy leads to pain and foot ulceration. Detecting neuropathy early may allow intervention with treatments to slow or reverse this condition (1). Recent studies suggested that small unmyelinated C-fibers are damaged early in diabetic neuropathy (2–4) but can only be detected using invasive procedures such as sural nerve biopsy (4,5) or skin-punch biopsy (6–8). Our studies have shown that corneal confocal microscopy (CCM) can identify early small nerve fiber damage and accurately quantify the severity of diabetic neuropathy (9–11). We have also shown that CCM relates to intraepidermal nerve fiber loss (12) and a reduction in corneal sensitivity (13) and detects early nerve fiber regeneration after pancreas transplantation (14). Recently we have also shown that CCM detects nerve fiber damage in patients with Fabry disease (15) and idiopathic small fiber neuropathy (16) when results of electrophysiology tests and quantitative sensory testing (QST) are normal. In this study we assessed corneal sensitivity and corneal nerve morphology using CCM in diabetic patients stratified for the severity of diabetic neuropathy using neurological evaluation, electrophysiology tests, and QST. This enabled us to compare CCM and corneal esthesiometry with established tests of diabetic neuropathy and define their sensitivity and specificity to detect diabetic patients with early neuropathy and those at risk of foot ulceration.

Bioactive SrO–SiO2 glass with well-ordered mesopores : characterization, physiochemistry and biological properties

For a biomaterial to be considered suitable for bone repair it should ideally be both bioactive and have a capacity for controllable drug delivery; as such, mesoporous SiO2 glass has been proposed as a new class of bone regeneration material by virtue of its high drug-loading ability and generally good biocompatibility. It does, however, have less than optimum bioactivity and controllable drug delivery properties. In this study, we incorporated strontium (Sr) into mesoporous SiO2 in an effort to develop a bioactive mesoporous SrO–SiO2 (Sr–Si) glass with the capacity to deliver Sr2+ ions, as well as a drug, at a controlled rate, thereby producing a material better suited for bone repair. The effects of Sr2+ on the structure, physiochemistry, drug delivery and biological properties of mesoporous Sr–Si glass were investigated. The prepared mesoporous Sr–Si glass was found to have an excellent release profile of bioactive Sr2+ ions and dexamethasone, and the incorporation of Sr2+ improved structural properties, such as mesopore size, pore volume and specific surface area, as well as rate of dissolution and protein adsorption. The mesoporous Sr–Si glass had no cytotoxic effects and its release of Sr2+ and SiO44− ions enhanced alkaline phosphatase activity – a marker of osteogenic cell differentiation – in human bone mesenchymal stem cells. Mesoporous Sr–Si glasses can be prepared to porous scaffolds which show a more sustained drug release. This study suggests that incorporating Sr2+ into mesoporous SiO2 glass produces a material with a more optimal drug delivery profile coupled with improved bioactivity, making it an excellent material for bone repair applications. Keywords: Mesoporous Sr–Si glass; Drug delivery; Bioactivity; Bone repair; Scaffolds

Vibrational spectroscopic study of the mineral tsumebite Pb2Cu(PO4,SO4) (OH)

The mineral tsumebite Pb2Cu(PO4)(SO4)(OH), a copper phosphate-sulfate hydroxide of the brackebuschite group has been characterised by Raman and infrared spectroscopy. The brackebuschite mineral group are a series of monoclinic arsenates, phosphates and vanadates of the general formula A2B(XO4)(OH,H2O), where A may be Ba, Ca, Pb, Sr, while B may be Al, Cu2+,Fe2+, Fe3+, Mn2+, Mn3+, Zn and XO4 may be AsO4, PO4, SO4,VO4. Bands are assigned to the stretching and bending modes of PO43- and HOPO3 units. Hydrogen bond distances are calculated based upon the position of the OH stretching vibrations and range from 2.759 Å to 3.205 Å. This range of hydrogen bonding contributes to the stability of the mineral.

An evaluation of the sustainability of agreements reached through mediations conducted by the dispute resolution centres of the Department of Justice and Attorney General, Queensland between 1999 to 2003

In 1990 the Dispute Resolution Centres Act, 1990 (Qld) (the Act) was passed by the Queensland Parliament. In the second reading speech for the Dispute Resolution Centres Bill on May 1990 the Hon Dean Wells stated that the proposed legislation would make mediation services available “in a non-coercive, voluntary forum where, with the help of trained mediators, the disputants will be assisted towards their own solutions to their disputes, thereby ensuring that the result is acceptable to the parties” (Hansard, 1990, 1718). It was recognised at that time that a method for resolving disputes was necessary for which “the conventional court system is not always equipped to provide lasting resolution” (Hansard, 1990, 1717). In particular, the lasting resolution of “disputes between people in continuing relationships” was seen as made possible through the new legislation; for example, “domestic disputes, disputes between employees, and neighbourhood disputes relating to such issues as overhanging tree branches, dividing fences, barking dogs, smoke, noise and other nuisances are occurring continually in the community” (Hansard, 1990, 1717). The key features of the proposed form of mediation in the Act were articulated as follows: “attendance of both parties at mediation sessions is voluntary; a party may withdraw at any time; mediation sessions will be conducted with as little formality and technicality as possible; the rules of evidence will not apply; any agreement reached is not enforceable in any court; although it could be made so if the parties chose to proceed that way; and the provisions of the Act do not affect any rights or remedies that a party to a dispute has apart from the Act” (Hansard, 1990, 1718). Since the introduction of the Act, the Alternative Dispute Resolution Branch of the Queensland Department of Justice and Attorney General has offered mediation services through, first the Community Justice Program (CJP), and then the Dispute Resolution Centres (DRCs) for a range of family, neighbourhood, workplace and community disputes. These services have mirrored those available through similar government agencies in other states such as the Community Justice Centres of NSW and the Victorian Dispute Resolution Centres. Since 1990, mediation has become one of the fastest growing forms of alternative dispute resolution (ADR). Sourdin has commented that "In addition to the growth in court-based and community-based dispute resolution schemes, ADR has been institutionalised and has grown within Australia and overseas” (2005, 14). In Australia, in particular, the development of ADR service provision “has been assisted by the creation and growth of professional organisations such as the Leading Edge Alternative Dispute Resolvers (LEADR), the Australian Commercial Dispute Centres (ACDC), Australian Disputes Resolution Association (ADRA), Conflict Resolution Network, and the Institute of Arbitrators and Mediators Australia (IAMA)” (Sourdin, 2005, 14). The increased emphasis on the use of ADR within education contexts (particularly secondary and tertiary contexts) has “also led to an increasing acceptance and understanding of (ADR) processes” (Sourdin, 2005, 14). Proponents of the mediation process, in particular, argue that much of its success derives from the inherent flexibility and creativity of the agreements reached through the mediation process and that it is a relatively low cost option in many cases (Menkel-Meadow, 1997, 417). It is also accepted that one of the main reasons for the success of mediation can be attributed to the high level of participation by the parties involved and thus creating a sense of ownership of, and commitment to, the terms of the agreement (Boulle, 2005, 65). These characteristics are associated with some of the core values of mediation, particularly as practised in community-based models as found at the DRCs. These core values include voluntary participation, party self-determination and party empowerment (Boulle, 2005, 65). For this reason mediation is argued as being an effective approach to resolving disputes, that creates a lasting resolution of the issues. Evaluation of the mediation process, particularly in the context of the growth of ADR, has been an important aspect of the development of the process (Sourdin, 2008). Writing in 2005 for example, Boulle, states that “although there is a constant refrain for more research into mediation practice, there has been a not insignificant amount of mediation measurement, both in Australia and overseas” (Boulle, 2005, 575). The positive claims of mediation have been supported to a significant degree by evaluations of the efficiency and effectiveness of the process. A common indicator of the effectiveness of mediation is the settlement rate achieved. High settlement rates for mediated disputes have been found for Australia (Altobelli, 2003) and internationally (Alexander, 2003). Boulle notes that mediation agreement rates claimed by service providers range from 55% to 92% (Boulle, 2005, 590). The annual reports for the Alternative Dispute Resolution Branch of the Queensland Department of Justice and Attorney-General considered prior to the commencement of this study indicated generally achievement of an approximate settlement figure of 86% by the Queensland Dispute Resolution Centres. More recently, the 2008-2009 annual report states that of the 2291 civil dispute mediated in 2007-2008, 86% reached an agreement. Further, of the 2693 civil disputes mediated in 2008-2009, 73% reached an agreement. These results are noted in the report as indicating “the effectiveness of mediation in resolving disputes” and as reflecting “the high level of agreement achieved for voluntary mediations” (Annual Report, 2008-2009, online). Whilst the settlement rates for the DRCs are strong, parties are rarely contacted for long term follow-up to assess whether agreements reached during mediation lasted to the satisfaction of each party. It has certainly been the case that the Dispute Resolution Centres of Queensland have not been resourced to conduct long-term follow-up assessments of mediation agreements. As Wade notes, "it is very difficult to compare "success" rates” and whilst “politicians want the comparison studies (they) usually do not want the delay and expense of accurate studies" (1998, 114). To date, therefore, it is fair to say that the efficiency of the mediation process has been evaluated but not necessarily its effectiveness. Rather, the practice at the Queensland DRCs has been to evaluate the quality of mediation service provision and of the practice of the mediation process. This has occurred, for example, through follow-up surveys of parties' satisfaction rates with the mediation service. In most other respects it is fair to say that the Centres have relied on the high settlement rates of the mediation process as a sign of the effectiveness of mediation (Annual Reports 1991 - 2010). Research of the mediation literature conducted for the purpose of this thesis has also indicated that there is little evaluative literature that provides an in-depth analysis and assessment of the longevity of mediated agreements. Instead evaluative studies of mediation tend to assess how mediation is conducted, or compare mediation with other conflict resolution options, or assess the agreement rate of mediations, including parties' levels of satisfaction with the service provision of the dispute resolution service provider (Boulle, 2005, Chapter 16).

Risk factors for Mycobacterium tuberculosis infection among children in Greenland

Objective To examine the risk factors for Mycobacterium tuberculosis infection (MTI) among Greenlandic children for the purpose of identifying those at highest risk of infection. Methods Between 2005 and 2007, 1797 Greenlandic schoolchildren in five different areas were tested for MTI with an interferon gamma release assay (IGRA) and a tuberculin skin test (TST). Parents or guardians were surveyed using a standardized self-administered questionnaire to obtain data on crowding in the household, parents’ educational level and the child’s health status. Demographic data for each child – i.e. parents’ place of birth, number of siblings, distance between siblings (next younger and next older), birth order and mother’s age when the child was born – were also extracted from a public registry. Logistic regression was used to check for associations between these variables and MTI, and all results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Children were considered to have MTI if they tested positive on both the IGRA assay and the TST. Findings The overall prevalence of MTI was 8.5% (152/1797). MTI was diagnosed in 26.7% of the children with a known TB contact, as opposed to 6.4% of the children without such contact. Overall, the MTI rate was higher among Inuit children (OR: 4.22; 95% CI: 1.55–11.5) and among children born less than one year after the birth of the next older sibling (OR: 2.48; 95% CI: 1.33–4.63). Self-reported TB contact modified the profile to include household crowding and low mother’s education. Children who had an older MTI-positive sibling were much more likely to test positive for MTI themselves (OR: 14.2; 95% CI: 5.75–35.0) than children without an infected older sibling. Conclusion Ethnicity, sibling relations, number of household residents and maternal level of education are factors associated with the risk of TB infection among children in Greenland. The strong household clustering of MTI suggests that family sources of exposure are important.

Isolation and functional characterisation of banana phytoene synthase genes as potential cisgenes

Carotenoids occur in all photosynthetic organisms where they protect photosystems from auto-oxidation, participate in photosynthetic energy-transfer and are secondary metabolites. Of the more than 600 known plant carotenoids, few can be converted into vitamin A by humans and so these pro-vitamin A carotenoids (pVAC) are important in human nutrition. Phytoene synthase (PSY) is a key enzyme in the biosynthetic pathway of pVACs and plays a central role in regulating pVAC accumulation in the edible portion of crop plants. Bananas are a major commercial crop and serve as a staple crop for more than 30 million people. There is natural variation in fruit pVAC content across different banana cultivars, but this is not well understood. Therefore, we isolated PSY genes from banana cultivars with relatively high (cv. Asupina) and low (cv. Cavendish) pVAC content. We provide evidence that PSY in banana is encoded by two paralogs (PSY1 and PSY2), each with a similar gene structure to homologous genes in other monocots. Further, we demonstrate that PSY2 is more highly expressed in fruit pulp compared to leaf. Functional analysis of PSY1 and PSY2 in rice callus and E. coli demonstrate that both genes encode functional enzymes, and that Asupina PSYs have approximately twice the enzymatic activity of the corresponding Cavendish PSYs. These results suggest that differences in PSY enzyme activity contribute significantly to the differences in Asupina and Cavendish fruit pVAC content. Importantly, Asupina PSY genes could potentially be used to generate new cisgenic or intragenic banana cultivars with enhanced pVAC content.

Evaluation of the Suchey-Brooks method for aging Australian Caucasian Populations using multislice Computed Tomography reconstructions of the Pubic Symphyseal Surface

Establishing age-at-death for skeletal remains is a vital component of forensic anthropology. The Suchey-Brooks (S-B) method of age estimation has been widely utilised since 1986 and relies on a visual assessment of the pubic symphyseal surface in comparison to a series of casts. Inter-population studies (Kimmerle et al., 2005; Djuric et al., 2007; Sakaue, 2006) demonstrate limitations of the S-B method, however, no assessment of this technique specific to Australian populations has been published. Aim: This investigation assessed the accuracy and applicability of the S-B method to an adult Australian Caucasian population by highlighting error rates associated with this technique. Methods: Computed tomography (CT) and contact scans of the S-B casts were performed; each geometrically modelled surface was extracted and quantified for reference purposes. A Queensland skeletal database for Caucasian remains aged 15 – 70 years was initiated at the Queensland Health Forensic and Scientific Services – Forensic Pathology Mortuary (n=350). Three-dimensional reconstruction of the bone surface using innovative volume visualisation protocols in Amira® and Rapidform® platforms was performed. Samples were allocated into 11 sub-sets of 5-year age intervals and changes associated with the surface geometry were quantified in relation to age, gender and asymmetry. Results: Preliminary results indicate that computational analysis was successfully applied to model morphological surface changes. Significant differences in observed versus actual ages were noted. Furthermore, initial morphological assessment demonstrates significant bilateral asymmetry of the pubic symphysis, which is unaccounted for in the S-B method. These results propose refinements to the S-B method, when applied to Australian casework. Conclusion: This investigation promises to transform anthropological analysis to be more quantitative and less invasive using CT imaging. The overarching goal contributes to improving skeletal identification and medico-legal death investigation in the coronial process by narrowing the range of age-at-death estimation in a biological profile.

The RNA world in plants: Post-transcriptional control III

Post-transcriptional control of gene expression has gone from a curiosity involving a few special genes to a highly diverse and widespread set of processes that is truly pervasive in plant gene expression. Thus, Plant Cell readers interested in almost any aspect of plant gene expression in response to any environmental influence, or in development, are advised to read on. In May 2001, what has become the de facto third biennial Symposium on Post-Transcriptional Control of Gene Expression in Plants was held in Ames, Iowa. The meeting was hosted by the new Plant Sciences Institute of Iowa State University with additional funding from the National Science Foundation and the United States Department of Agriculture. In 1997, the annual University of California-Riverside Plant Physiology Symposium was devoted to this topic. This provided a wake-up call to the plant world, summarized in this journal (Gallie and Bailey-Serres, 1997), that not all gene expression is controlled at the level of transcription. This was expanded upon at a European Molecular Biology Organization Workshop in Leysin, Switzerland, in 1999 (Bailey-Serres et al., 1999). The 3-day meeting in Ames brought together a strong and diverse contingent of plant biologists from four continents. The participants represented an unusually heterogeneous group of disciplines ranging from virology to stress response to computational biology. The research approaches and techniques represented were similarly diverse. Here we discuss a sample of the many fascinating aspects of post-transcriptional control that were presented at this meeting; we apologize to those whose work is not described here.

Fibrogenic stresses activate different mitogen-activated protein kinase pathways in renal epithelial, endothelial or fibroblast cell populations

Fibrogenic stresses promote progression of renal tubulointerstitial fibrosis, disparately affecting survival, proliferation and trans-differentiation of intrinsic renal cell populations through ill-defined biomolecular pathways. We investigated the effect of fibrogenic stresses on the activation of cell-specific mitogen-activated protein kinase (MAPK) in renal fibroblast, epithelial and endothelial cell populations. The relative outcomes (cell death, proliferation, trans-differentiation) associated with activation or inhibition of extracellular-regulated protein kinase (ERK) or stress activated/c-Jun N terminal kinase (JNK) were analysed in each renal cell population after challenge with oxidative stress (1 mmol/L H2O2), transforming growth factor-beta1 (TGF-beta1, 10 ng/mL) or tumour necrosis factor-alpha (TNF-alpha, 50 ng/mL) over 0-20 h. Apoptosis increased significantly in all cell types after oxidative stress (P < 0.05). In fibroblasts, oxidative stress caused the activation of ERK (pERK) but not JNK (pJNK). Inhibition of ERK by PD98059 supported its role in a fibroblast death pathway. In epithelial and endothelial cells, oxidative stress-induced apoptosis was preceded by early induction of pERK, but its inhibition did not support a pro-apoptotic role. Early ERK activity may be conducive to their survival or promote the trans-differentiation of epithelial cells. In epithelial and endothelial cells, oxidative stress induced pJNK acutely. Pretreatment with SP600125 (JNK inhibitor) verified its pro-apoptotic activity only in epithelial cells. Transforming growth factor-beta1 did not significantly alter mitosis or apoptosis in any of the cell types, nor did it alter MAPK activity. Tumor necrosis factor-alpha caused increased apoptosis with no associated change in MAPK activity. Our results demonstrate renal cell-specific differences in the activation of ERK and JNK following fibrotic insult, which may be useful for targeting excessive fibroblast proliferation in chronic fibrosis.

Household food insecurity is associated with less physical activity among children and adults in the U.S. population

Background Household food insecurity and physical activity are each important public-health concerns in the United States, but the relation between them was not investigated thoroughly. Objective We wanted to examine the association between food insecurity and physical activity in the U.S. population. Methods Physical activity measured by accelerometry (PAM) and physical activity measured by questionnaire (PAQ) data from the NHANES 2003–2006 were used. Individuals aged <6 y or >65 y, pregnant, with physical limitations, or with family income >350% of the poverty line were excluded. Food insecurity was measured by the USDA Household Food Security Survey Module. Adjusted ORs were calculated from logistic regression to identify the association between food insecurity and adherence to the physical-activity guidelines. Adjusted coefficients were obtained from linear regression to identify the association between food insecurity with sedentary/physical-activity minutes. Results In children, food insecurity was not associated with adherence to physical-activity guidelines measured via PAM or PAQ and with sedentary minutes (P > 0.05). Food-insecure children did less moderate to vigorous physical activity than food-secure children (adjusted coefficient = −5.24, P = 0.02). In adults, food insecurity was significantly associated with adherence to physical-activity guidelines (adjusted OR = 0.72, P = 0.03 for PAM; and OR = 0.84, P < 0.01 for PAQ) but was not associated with sedentary minutes (P > 0.05). Conclusion Food-insecure children did less moderate to vigorous physical activity, and food-insecure adults were less likely to adhere to the physical-activity guidelines than those without food insecurity.

Correlation between architectural variables and torque in the erector spinae muscle during maximal isometric contraction

This study analysed whether a significant relationship exists between the torque and muscle thickness and pennation angle of the erector spinae muscle during a maximal isometric lumbar extension with the lumbar spine in neutral position. This was a cross-sectional study in which 46 healthy adults performed three repetitions for 5 s of maximal isometric lumbar extension with rests of 90 s. During the lumbar extensions, bilateral ultrasound images of the erector spinae muscle (to measure pennation angle and muscle thickness) and torque were acquired. Reliability test analysis calculating the internal consistency (Cronbach's alpha) of the measure, correlation between pennation angle, muscle thickness and torque extensions were examined. Through a linear regression the contribution of each independent variable (muscle thickness and pennation angle) to the variation of the dependent variable (torque) was calculated. The results of the reliability test were: 0.976–0.979 (pennation angle), 0.980–0.980 (muscle thickness) and 0.994 (torque). The results show that pennation angle and muscle thickness were significantly related to each other with a range between 0.295 and 0.762. In addition, multiple regression analysis showed that the two variables considered in this study explained 68% of the variance in the torque. Pennation angle and muscle thickness have a moderate impact on the variance exerted on the torque during a maximal isometric lumbar extension with the lumbar spine in neutral position.

Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population

Background: The genome-wide association study era has made great progress in identifying susceptibility genes and genetic loci for rheumatoid arthritis (RA) in populations of White European ancestry. However, few studies have tried to dissect disease aetiopathogenesis in other ethnic populations. Objective: To investigate these associations in the Han Chinese population. Methods: Haplotypes from the HapMap database Chinese population were used to select tag-single-nucleotide polymorphisms (SNPs) (r2 =0.8) across 19 distinct RA genomic regions. A two phase case-control association study was performed, with 169 SNPs genotyped in phase I (n=571 cases, n=880 controls), and 64 SNPs achieving p<0.2 in the first phase being genotyped in phase II (n=464 cases, n=822 controls). Association statistics were calculated using permutation tests both unadjusted and adjusted for the number of markers studied. Results: Robust association was detected for MMEL1 and CTLA4 , and modest association was identified for another six loci: PADI4 , STAT4 , PRDM1 , CDK6 , TRAF1-C5 and KIF5A-PIP4K2C. All three markers genotyped in MMEL1 demonstrated association, with peak signal for rs3890745 (p=2.6×10 -5unadjusted, p=0.003 adjusted, OR=0.79). For CTLA4 , significance was detected for three of five variants showing association, with peak association for marker rs12992492 (p=4.3×10-5 unadjusted, p=0.0021 adjusted, OR=0.77). Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed. Conclusion: This study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations. It also confirms the value of multiethnic population studies to help dissect disease aetiopathogenesis.