title: A genome-wide association study of total serum and mite-specific IgEs in asthma patients.
abstract: Immunoglobulin E (IgE) is one of the central players in asthma and allergic diseases. Although the serum IgE level, a useful endophenotype, is generally increased in patients with asthma, genetic factors influencing IgE regulation in asthma are still not fully understood. To identify the genetic variations associated with total serum and mite-specific IgEs in asthmatics, a genome-wide association study (GWAS) of 657,366 single nucleotide polymorphisms (SNPs) was performed in 877 Korean asthmatics. This study found that several new genes might be associated with total IgE in asthmatics, such as CRIM1 (rs848512, P = 1.18×10(-6); rs711254, P = 6.73×10(-6)), ZNF71 (rs10404342, P = 7.60×10(-6)), TLN1 (rs4879926, P = 7.74×10(-6)), and SYNPO2 (rs1472066, P = 8.36×10(-6); rs1038770, P = 8.66×10(-6)). Regarding the association of specific IgE to house dust mites, it was observed that intergenic SNPs nearby to OPRK1 and LOC730217 might be associated with Dermatophagoides pteronyssinus (D.p.) and Dermatophagoides farinae (D.f.) in asthmatics, respectively. In further pathway analysis, the phosphatidylinositol signaling system and adherens junction pathways were estimated to play a role in the regulation of total IgE levels in asthma. Although functional evaluations and replications of these results in other populations are needed, this GWAS of serum IgE in asthmatics could facilitate improved understanding of the role of the newly identified genetic variants in asthma and its related phenotypes.
authors: Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors: Jeong-Hyun
authors: JH
authors: Kim
authors: Hyun Sub
authors: HS
authors: Cheong
authors: Jong Sook
authors: JS
authors: Park
authors: An-Soo
authors: AS
authors: Jang
authors: Soo-Taek
authors: ST
authors: Uh
authors: Yong-Hoon
authors: YH
authors: Kim
authors: Mi-Kyeong
authors: MK
authors: Kim
authors: Inseon S
authors: IS
authors: Choi
authors: Sang Heon
authors: SH
authors: Cho
authors: Byoung Whui
authors: BW
authors: Choi
authors: Joon Seol
authors: JS
authors: Bae
authors: Choon-Sik
authors: CS
authors: Park
authors: Hyoung Doo
authors: HD
authors: Shin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D002648:Child; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D039981:Pyroglyphidae / Q000276:immunology*; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D039741:Antigens, Dermatophagoides; D007073:Immunoglobulin E
references: J Allergy Clin Immunol. 2002 Nov;110(5):743-51
references: 12417883
references: N Engl J Med. 1991 Oct 10;325(15):1067-71
references: 1891008
references: Proc Natl Acad Sci U S A. 1989 Dec;86(24):10085-9
references: 2513574
references: Ann Allergy. 1991 Sep;67(3):365-70
references: 1897816
references: Allergy. 2012 Jan;67(1):67-73
references: 21958117
references: N Engl J Med. 1989 Feb 2;320(5):271-7
references: 2911321
references: Curr Opin Pulm Med. 2012 Jan;18(1):29-34
references: 22081090
references: Respiration. 2010;79(1):17-24
references: 19672052
references: Int Immunol. 2008 Apr;20(4):499-508
references: 18303010
references: Genes Immun. 2008 Apr;9(3):224-30
references: 18340359
references: Science. 2004 Apr 9;304(5668):300-4
references: 15073379
references: Nat Rev Immunol. 2008 Mar;8(3):205-17
references: 18301424
references: Nucleic Acids Res. 2009 May;37(9):e67
references: 19339519
references: Nat Rev Immunol. 2008 Mar;8(3):218-30
references: 18274559
references: Annu Rev Med. 2007;58:185-203
references: 17059361
references: Nat Rev Genet. 2009 Apr;10(4):241-51
references: 19293820
references: Eur Respir J. 1996 Sep;9(9):1880-4
references: 8880106
references: Genome Res. 2007 Oct;17(10):1537-45
references: 17785539
references: Arch Med Res. 2007 Jan;38(1):99-105
references: 17174732
references: Am J Respir Crit Care Med. 2009 Jun 15;179(12):1084-90
references: 19264973
references: J Allergy Clin Immunol. 2013 Apr;131(4):1176-84
references: 23146381
references: Allergy Asthma Immunol Res. 2011 Oct;3(4):236-44
references: 21966603
references: J Allergy Clin Immunol. 2004 Mar;113(3):489-95
references: 15007352
references: N Engl J Med. 2010 Sep 23;363(13):1211-1221
references: 20860503
references: Clin Exp Allergy. 2009 Oct;39(10):1558-68
references: 19624525
references: J Allergy Clin Immunol. 1996 Jul;98(1):172-80
references: 8765832
references: Eur Respir J. 2010 Jan;35(1):54-63
references: 19574333
references: Clin Exp Allergy. 2009 Jan;39(1):101-9
references: 19016802
references: Nat Genet. 2006 Feb;38(2):209-13
references: 16415888
references: Respir Res. 2002;3:7
references: 11806842
references: J Allergy Clin Immunol. 2012 Feb;129(2):573-5, 575.e1-10
references: 22070913
references: Nat Rev Immunol. 2006 Mar;6(3):218-30
references: 16470226
references: J Allergy Clin Immunol. 2006 Feb;117(2):269-74
references: 16461126
references: J Allergy Clin Immunol. 2012 Mar;129(3):840-845.e21
references: 22075330
references: Curr Opin Allergy Clin Immunol. 2009 Apr;9(2):128-35
references: 19326507
references: Nat Genet. 2006 Aug;38(8):904-9
references: 16862161
references: Am J Respir Crit Care Med. 2013 May 15;187(10):1076-84
references: 23491407
references: J Allergy Clin Immunol. 2012 Feb;129(2):575-8, 578.e1-9
references: 22070912
references: Clin Exp Immunol. 2005 Jul;141(1):122-9
references: 15958078
references: PLoS Genet. 2008 Aug;4(8):e1000166
references: 18846228
references: Am J Hum Genet. 2007 Jun;80(6):1103-14
references: 17503328
references: Am J Hum Genet. 2000 Nov;67(5):1163-73
references: 11023809