Number of classical HLA alleles and polymorphic amino acid positions in the HLA reference panel.

<p>Number of classical HLA alleles and polymorphic amino acid positions in the HLA reference panel.</p

Frequencies and disease effect sizes of imputed and genotyped <i>HLA-DRB1</i> alleles.

<p>We revisited our previous rheumatoid arthritis association studies using either typed SNPs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112546#pone.0112546-Kim1" target="_blank">[16]</a> or HLA alleles <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112546#pone.0112546-Bang1" target="_blank">[17]</a>. After imputing HLA variants from the SNP-based dataset, (A) frequencies and (B) disease effect sizes of the imputed classical alleles of <i>HLA-DRB1</i> were compared with those of genotyped classical alleles in the HLA-based dataset.</p

Concordance rates between imputed and genotyped alleles.

<p>* Reference panel and test datasets were randomly assigned 100 times from all 413 Korean subjects and the mean concordance rate was calculated by 100 independent imputations using each of the 100 reference panel and test dataset pairs.</p><p>** For consistency of panel size between Korean and European panels, the mean concordance rate was calculated by 100 independent imputations using 100 different subsets (n = 413) of the European reference panel.</p><p>Concordance rates between imputed and genotyped alleles.</p

Concordance rates using various reference panels.

<p>SNPs present in 9 different commercial arrays were extracted for imputing the HLA alleles from the HapMap3 r2 dataset of East Asian (CHB + JPT) individuals. Each subset was imputed for <i>HLA-A</i>, <i>-B</i>, <i>-C</i>, <i>-DQB1</i> and <i>-DRB1</i> using the Korean reference panel. Concordance rates (y-axis) were plotted against the proportion of reference-panel SNPs that were present in each subset (x-axis).</p

Additional file 1: of The beneficial effects of Tai Chi exercise on endothelial function and arterial stiffness in elderly women with rheumatoid arthritis

Correlation plot of change in flow-mediated dilatation (FMD) versus change in brachial-ankle pulse wave velocity (baPWV) after 3 months of Tai Chi exercise. (JPG 337 kb

Additional file 1: Table S1. of Biological function integrated prediction of severe radiographic progression in rheumatoid arthritis: a nested case control study

Characteristics of study populations. Table S2. GWAS results for severe radiographic progression (p <1.0 × 10–3). Table S3. List of the top 85 SNPs and their related genes selected by a post-GWAS approach. Table S4 Sensitivity, specificity, and positive predictive value of the final models. (DOCX 77 kb

Bone Morphogenetic Protein 6 Polymorphisms Are Associated with Radiographic Progression in Ankylosing Spondylitis

<div><p>Background and Object</p><p>Nearly 25 genetic loci associated with susceptibility to ankylosing spondylitis (AS) have been identified by several large studies. However, there have been limited studies to identify the genes associated with radiographic severity of the disease. Thus we investigated which genes involved in bone formation pathways might be associated with radiographic severity in AS.</p><p>Methods</p><p>A total of 417 Korean AS patients were classified into two groups based on the radiographic severity as defined by the modified Stoke’ Ankylosing Spondylitis Spinal Score (mSASSS) system. Severe AS was defined by the presence of syndesmophytes and/or fusion in the lumbar or cervical spine (n = 195). Mild AS was defined by the absence of any syndesmophyte or fusion (n = 170). A total of 251 single nucleotide polymorphisms (SNPs) within 52 genes related to bone formation were selected and genotyped. Odds ratios (OR) and 95% confidence interval (95% CI) were analysed by multivariate logistic regression controlling for age at onset of symptoms, sex, disease duration, and smoking status as covariates.</p><p>Results</p><p>We identified new loci of bone morphogenetic protein 6 (<i>BMP6</i>) associated with radiographic severity in patients with AS that passed false discovery rate threshold. Two SNPs in <i>BMP6</i> were significantly associated with radiologic severity [r<i>s270378</i> (OR 1.97, p = 6.74×10⁻⁴) and <i>rs1235192</i> [OR 1.92, p = 1.17×10⁻³]) adjusted by covariates.</p><p>Conclusion</p><p>This is the first study to demonstrate that <i>BMP6</i> is associated with radiographic severity in AS, supporting the role wingless-type like/BMP pathway on radiographic progression in AS.</p></div

Clinical characteristics of study cohort.

<p>Data were shown to mean ± SD or n (%).</p><p>*Continuous NSAID intake was defined as 70 or more the score. AS; ankylosing spondylitis, HLA-B27: human leukocyte antigen-B27; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; Msasss: modified stokes AS spine score; NSAID: non-steroidal anti-inflammatory drugs.</p

Significant association between polymorphism associated with bone formation in AS patients.

<p>AS: ankylosing spondylitis; SNP: single nucleotide polymorphism; Chr: chromosome; Freq: frequency; OR: odds ratio; CI: confidence interval; FDR: false discovery rate; BMP6: bone morphogenetic protein 6.</p

Additional file 1: Table S1. of An HLA-C amino-acid variant in addition to HLA-B*27 confers risk for ankylosing spondylitis in the Korean population

Effect estimates for each residue at HLA-B amino-acid positions 70, 97, and 114. Table S2. Association of HLA-B amino-acid position 97 with ankylosing spondylitis in Korean and European populations. (PDF 84 kb