title: High-density genotyping of immune loci in Kawasaki disease and IVIG treatment response in European-American case-parent trio study.
abstract: Kawasaki disease (KD) is a diffuse and acute small-vessel vasculitis observed in children, and has genetic and autoimmune components. We genotyped 112 case-parent trios of European decent (confirmed by ancestry informative markers) using the immunoChip array, and performed association analyses with susceptibility to KD and intravenous immunoglobulin (IVIG) non-response. KD susceptibility was assessed using the transmission disequilibrium test, whereas IVIG non-response was evaluated using multivariable logistic regression analysis. We replicated single-nucleotide polymorphisms (SNPs) in three gene regions (FCGR, CD40/CDH22 and HLA-DQB2/HLA-DOB) that have been previously associated with KD and provide support to other findings of several novel SNPs in genes with a potential pathway in KD pathogenesis. SNP rs838143 in the 3'-untranslated region of the FUT1 gene (2.7 × 10(-5)) and rs9847915 in the intergenic region of LOC730109 | BRD7P2 (6.81 × 10(-7)) were the top hits for KD susceptibility in additive and dominant models, respectively. The top hits for IVIG responsiveness were rs1200332 in the intergenic region of BAZ1A | C14orf19 (1.4 × 10(-4)) and rs4889606 in the intron of the STX1B gene (6.95 × 10(-5)) in additive and dominant models, respectively. Our study suggests that genes and biological pathways involved in autoimmune diseases have an important role in the pathogenesis of KD and IVIG response mechanism.
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Shendre
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Wiener
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: D
authors.initials: D
authors.lastname: Zhi
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: A I
authors.initials: AI
authors.lastname: Vazquez
authors.affiliation: Department of Pediatrics, University of Washington, Seattle Children's Research Institute, Seattle, WA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Portman
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shrestha
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007223:Infant; D007438:Introns / Q000235:genetics; D016015:Logistic Models; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D015999:Multivariate Analysis; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D050827:Syntaxin 1 / Q000235:genetics; D016896:Treatment Outcome; D014481:United States; D044465:White People / Q000235:genetics; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D020413:3' Untranslated Regions; D005647:Fucosyltransferases; D016756:Immunoglobulins, Intravenous; D050827:Syntaxin 1; D000097631:Galactoside 2-alpha-L-fucosyltransferase
references.citation: Nucleic Acids Res. 2011 Oct;39(19):8445-56
references.pmid: 21745822
references.citation: Circulation. 2004 Oct 26;110(17):2747-71
references.pmid: 15505111
references.citation: Hawaii Med J. 2010 Aug;69(8):194-7
references.pmid: 20845285
references.citation: J Pediatr. 2013 Jul;163(1):126-31.e1
references.pmid: 23312687
references.citation: Cardiovasc Res. 2011 Nov 1;92(2):247-55
references.pmid: 21771897
references.citation: Arerugi. 1967 Mar;16(3):178-222
references.pmid: 6062087
references.citation: Pediatr Infect Dis J. 2005 Nov;24(11):998-1004
references.pmid: 16282937
references.citation: Nat Genet. 2006 Aug;38(8):904-9
references.pmid: 16862161
references.citation: Exp Hematol. 2008 Sep;36(9):1205-15
references.pmid: 18550258
references.citation: J Cell Physiol. 2008 Apr;215(1):27-36
references.pmid: 18205178
references.citation: Mol Hum Reprod. 2012 Apr;18(4):204-15
references.pmid: 22053055
references.citation: Circ J. 2012;76(7):1581-6
references.pmid: 22789975
references.citation: J Am Acad Dermatol. 2013 Oct;69(4):513.e1-8; quiz 521-2
references.pmid: 24034380
references.citation: Mol Immunol. 2008 Apr;45(8):2401-10
references.pmid: 18155296
references.citation: PLoS Genet. 2010 Oct 28;6(10):e1001184
references.pmid: 21060863
references.citation: Genomics. 1996 Sep 15;36(3):551-3
references.pmid: 8884284
references.citation: Science. 1992 Jul 10;257(5067):255-9
references.pmid: 1321498
references.citation: Pediatrics. 2003 Feb;111(2):E140-7
references.pmid: 12563087
references.citation: Cytokine. 1996 Mar;8(3):183-9
references.pmid: 8833032
references.citation: Tumour Biol. 2009;30(3):130-40
references.pmid: 19546606
references.citation: Am J Med Genet. 2002 Jul 8;114(5):497-508
references.pmid: 12116183
references.citation: Arch Pediatr Adolesc Med. 2004 Dec;158(12):1166-9
references.pmid: 15583102
references.citation: Hum Genet. 2013 Jun;132(6):669-80
references.pmid: 23456091
references.citation: Nat Rev Genet. 2013 Sep;14(9):661-73
references.pmid: 23917628
references.citation: Cell Physiol Biochem. 2003;13(2):75-84
references.pmid: 12649592
references.citation: Biochem Biophys Res Commun. 2013 Oct 11;440(1):163-7
references.pmid: 24055037
references.citation: PLoS Genet. 2013;9(1):e1003201
references.pmid: 23341781
references.citation: Dev Biol. 2009 May 15;329(2):269-79
references.pmid: 19272373
references.citation: Genes Immun. 2007 Sep;8(6):513-7
references.pmid: 17581627
references.citation: Circ Cardiovasc Genet. 2012 Jun;5(3):309-16
references.pmid: 22565545
references.citation: J Leukoc Biol. 2014 Feb;95(2):305-12
references.pmid: 24146186
references.citation: Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H1053-64
references.pmid: 17483238
references.citation: Acta Pharmacol Sin. 2011 Oct;32(10):1193-8
references.pmid: 21892198
references.citation: Pharmacogenet Genomics. 2013 Sep;23(9):455-62
references.pmid: 23778324
references.citation: Transpl Immunol. 2012 Dec;27(4):151-6
references.pmid: 23063462
references.citation: J Allergy Clin Immunol. 2011 Sep;128(3):677-80
references.pmid: 21601260
references.citation: Nat Genet. 2011 Nov 13;43(12):1241-6
references.pmid: 22081228
references.citation: Pediatr Rheumatol Online J. 2013 Sep 05;11(1):32
references.pmid: 24006904
references.citation: Arthritis Res Ther. 2011 Feb 01;13(1):101
references.pmid: 21345260
references.citation: Tissue Antigens. 1993 Sep;42(3):153-5
references.pmid: 8284790
references.citation: Hum Immunol. 1995 Mar;42(3):195-202
references.pmid: 7759306
references.citation: Circ J. 2010 Mar;74(3):544-51
references.pmid: 20081319
references.citation: Hum Mutat. 2000 Nov;16(5):448
references.pmid: 11058912
references.citation: Dev Cell. 2011 Apr 19;20(4):526-39
references.pmid: 21396893
references.citation: Immunogenetics. 2013 Oct;65(10):703-9
references.pmid: 23836313
references.citation: Clin Exp Rheumatol. 1994 Jan-Feb;12(1):29-33
references.pmid: 8162639
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: Arthritis Res Ther. 2014 Jan 28;16(1):R28
references.pmid: 24467809
references.citation: J Hypertens. 2010 Nov;28(11):2219-26
references.pmid: 20683337
references.citation: Nat Genet. 2010 Dec;42(12):1118-25
references.pmid: 21102463
references.citation: PLoS Genet. 2011 Aug;7(8):e1002197
references.pmid: 21829388
references.citation: Biochim Biophys Acta. 2008 Feb;1783(2):287-96
references.pmid: 18023290
references.citation: Nat Genet. 2012 Mar 25;44(5):502-10
references.pmid: 22446964