Analysis of susceptibility loci for juvenile idiopathic arthritis in the extended Mhc region using high resolution Snp and Hla allele typing

• Autorzy: Biesiada J. , Sudman M. , Wagner M. , Rupert A. , Hollenbach J. , Haas J. P. , Meller J. , Thompson S. D.
• Języki publikacji: EN

Abstrakty

EN

Juvenile idiopathic arthritis ( JIA ) spans several pediatric arthropathies that involve autoimmune responses. Primary genetic risk factors for JIA have been mapped to Major Histocompatibility Complex ( MHC ) class I and class II genes. Recent genome-wide association studies using SNP arrays have shown that the nonHLA genetic component of JIA involves multiple low-risk loci, reinforcing the notion that JIA is a complex genetic trait with a strong HLA component. In this work, with the goal of detailed mapping and analysis of lin kage disequilibrium ( LD ) patterns and associations with JIA in the extended MHC (x MHC ) region, we combined SNP data from Affymetrix SNP Array 6.0 and Immunochip ( IC ) platforms with high resolution typing of 8 classical HLA genes. A cohort of about 800 affected individuals and about 500 ethnically matched controls from the Cincinnati region, as well as secondary validation cohorts of affected individuals and matched controls from Germany were used to perform the an alysis, and to assess reproducibility of the results across different platforms and p opulations. Accurate high resolution maps of linkage with classical HLA genes and association with individual HLA alleles were generated. High concordance of results obtained using Affymetrix SNP Array 6.0 and IC was observed, with an additional resolution and improved mapping of associat ions provided by the latter in some regions. Several new peaks of statistically signific ant and reproducible association with JIA outside the regions of strong LD with classical HLA genes were observed, including one peak in the class III region, and one in the telomeric end of x MHC . Conditional analysis provided further evidence that these associations appear t o be independent of classical HLA genes studied here. The results and observed association patterns ar e further discussed in the context of other recent studies on autoimmune diseases, includin g the role of HLA DRB 1 in adult Rheumatoid Arthritis.

Słowa kluczowe

EN

HLA; MHC region; autoimmunology; SNP genotype

PL

HLA; MHC region; autoimmunologia; HLA niezależna asocjacja; SNP genotyp

• Wydawca: Politechnika Gdańska
• Czasopismo: TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk
• Rocznik: 2014
• Tom: Vol. 18, No 4
• Strony: 305--320
• Opis fizyczny: Bibliogr. 24 poz., rys., wykr., tab.

Twórcy

autor

Biesiada J.

• Biomedical Informatics, Children’s Hospital Research Foun dation 3333 Burnet Avenue, Cincinnati, OH 45229, USA

autor

Sudman M.

• Center for Autoimmune Genomics and Etiology Cincinnati Children’s Hospital Medical Center 3333 Burnet Avenue, Cincinnati, OH 45229, USA
• Division of Rheumatology, Cincinnati Children’s Hospital Me dical Center 3333 Burnet Avenue, Cincinnati, OH 45229, USA

autor

Wagner M.

• Biomedical Informatics, Children’s Hospital Research Foun dation 3333 Burnet Avenue, Cincinnati, OH 45229, USA

autor

Rupert A.

• Biomedical Informatics, Children’s Hospital Research Foun dation 3333 Burnet Avenue, Cincinnati, OH 45229, USA

autor

Hollenbach J.

• Department of Neurology, University of California 675 Nelson Rising Lane, San Francisco CA 94143, USA

autor

Haas J. P.

• German Centre for Rheumatology in Children and Young People Gehfeldstr. 24, 82467 Garmisch-Partenkirchen, Germany

autor

Meller J.

• Biomedical Informatics, Children’s Hospital Research Foun dation 3333 Burnet Avenue, Cincinnati, OH 45229, USA
• Department of Environmental Health, University of Cincinna ti PO Box 670056, Cincinnati, Ohio 45267-0056, USA
• Department of Informatics, Nicolaus Copernicus University Grudziadzka 5, 87-100 Torun, Poland

autor

Thompson S. D.

• Center for Autoimmune Genomics and Etiology Cincinnati Children’s Hospital Medical Center 3333 Burnet Avenue, Cincinnati, OH 45229, USA
• Division of Rheumatology, Cincinnati Children’s Hospital Me dical Center 3333 Burnet Avenue, Cincinnati, OH 45229, USA

Bibliografia

• [1] Petty R E, Southwood T R, Manners P, Baum J, Glass D N, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur A M et al. 2004 J. Rheumatol. 31 390
• [2] Cassidy J T and Petty R E 2005 In Textbook of Pediatric Rheumatology , Cassidy J T and Petty R E (eds.), WB Saunders 808
• [3] Prahalad S, Shear E S, Thompson S D, Giannini E H and Glass D N 2002 Arthritis Rheum. 46 1851
• [4] Saurenmann R K, Rose J B, Tyrrell P, Feldman B M, Laxer R M, Schneider R and Silverman E D 2007 Arthritis Rheum. 56 1974
• [5] Hollenbach J, Thompson S D, Bugawan T, Ryan M, Sudman M, Marion M, Langefeld C, Thomson G, Erlich H and Glass D N 2010 Arthritis Rheum. 62 1781
• [6] Murray K J, Moroldo M B, Donnelly P, Prahalad S, Passo M H, Giannini E H and Glass D N 1999 Arthritis Rheum. 42 1843
• [7] Prahalad S, Ryan M H, Shear E S, Thompson S D, Giannini E H and Glass D N 2000 Arthritis Rheum. 43 2335
• [8] Behrens E M, Finkel T H, Bradfield J P, Kim C E, Linton L, Casalunovo T, Frackel-ton E C, Santa E, Otieno F G, Glessner J T et al. 2008 Arthritis Rheum. 58 2206
• [9] Hinks A, Barton A, Shephard N, Eyre S, Bowes J, Cargill M, Wang E, Ke X, Kennedy G C, John S et al. 2009 Arthritis Rheum. 60 258
• [10] Prahalad S, Hansen S, Whiting A, Guthery S L, Clifford B, McNally B, Zeft A S, Bohnsack J F and Jorde L B 2009 Arthritis Rheum. 60 2124
• [11] Hinks A, Eyre S, Ke X, Barton A, Martin P, Flynn E, Packham J, Worthington J and Thomson W 2009 Ann. Rheum. Dis. , ard.2009.110650
• [12] Thompson S D, Sudman M, Ramos P S, Marion M C, Ryan M, Tsoras M, Weiler T, Wagner M, Keddache M, Haas J P et al. 2010 Arthritis Rheum. 62 3265
• [13] Stahl E A, Raychaudhuri S, Remmers E F, Xie G, Eyre S, Thomson B P, Li Y, Kurreeman F A, Zhernakova A, Hinks A et al. 2010 Nat. Genet. 42 508
• [14] Reveille J D, Sims A M, Danoy P, Evans D M, Leo P, Pointon J J, Jin R, Zhou X, Bradbury L A, Appleton L H et al. 2010 Nat. Genet. 42 123
• [15] Stuart P E, Nair R P, Ellinghaus E, Ding J, Tejasvi T, Gudjonsson J E, Li Y, Weidinger S, Eberlein B, Gieger C et al. 2010 Nat. Genet. 42 1000
• [16] Ma W, Du J, Chu Q, Wang Y, Liu L, Song M and Wang W 2011 Biochem. Biophys. Res. Commun. 408 84
• [17] Orozco G, Eyre S, Hinks A, Bowes J, Morgan A W, Wilson A G, Wordsworth P, Steer S, Hocking L, Thomson W et al. 2011 Ann. Rheum. Dis. 70 463
• [18] Hinks A, Cobb J, Marion M C, Prahalad S, Sudman M et al. 2013 Nature Genetics 45 664
• [19] Stephens M, Smith N J and Donnelly P 2001 Am. J. Hum. Genet. 68 (4) 978
• [20] Lin S, Qin Z S, Munro H M, Abecasis G R and Donnelly P 2006 J. Hum. Genet. 78 ( 3 ) 437
• [21] de Bakker P I, McVean G, Sabeti P C, Miretti M M, Green T, Marchini J, Ke X, Monsuur A J, Whittaker P, Delgado M et al. 2006 Nat. Genet. 38 1166
• [22] The International HapMap Consortium 2010 Nature 467 52
• [23] Raychaudhuri S et al. 2012 Nat. Genet. 44 (3) 291
• [24] Leslie S et al. 2008 Am. J. Hum. Genet. 82 (1) 48