The genetic basis of autoantibody production is largely unknown outside of associations located in the major histocompatibility complex (MHC) human leukocyte antigen (HLA) region. The aim of this study is the discovery of new genetic associations with autoantibody positivity using genome-wide association scan single nucleotide polymorphism (SNP) data in type 1 diabetes (T1D) patients with autoantibody measurements. We measured two anti-islet autoantibodies, glutamate decarboxylase (GADA, n = 2,506), insulinoma-associated antigen 2 (IA-2A, n = 2,498), antibodies to the autoimmune thyroid (Graves') disease (AITD) autoantigen thyroid peroxidase (TPOA, n = 8,300), and antibodies against gastric parietal cells (PCA, n = 4,328) that are associated with autoimmune gastritis. Two loci passed a stringent genome-wide significance level (p<10−10): 1q23/FCRL3 with IA-2A and 9q34/ABO with PCA. Eleven of 52 non-MHC T1D loci showed evidence of association with at least one autoantibody at a false discovery rate of 16%: 16p11/IL27-IA-2A, 2q24/IFIH1-IA-2A and PCA, 2q32/STAT4-TPOA, 10p15/IL2RA-GADA, 6q15/BACH2-TPOA, 21q22/UBASH3A-TPOA, 1p13/PTPN22-TPOA, 2q33/CTLA4-TPOA, 4q27/IL2/TPOA, 15q14/RASGRP1/TPOA, and 12q24/SH2B3-GADA and TPOA. Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A).
Vyšlo v časopise: Genome-Wide Association Analysis of Autoantibody Positivity in Type 1 Diabetes Cases. PLoS Genet 7(8): e32767. doi:10.1371/journal.pgen.1002216 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002216
1. SavolaKSabbahEKulmalaPVähäsaloPIlonenJ 1998 Autoantibodies associated with Type I diabetes mellitus persist after diagnosis in children. Diabetologia 41 1293 1297
2. KnipMKorhonenSKulmalaPVeijolaRReunanenA 2010 Prediction of Type 1 Diabetes in the General Population. Diabetes Care 33 1206 1212
3. WongSWenLTangMRamanathanMVisintinI 2004 Investigation of the role of B-cells in type 1 diabetes in the NOD mouse. Diabetes 53 2581 2587
4. PescovitzMGreenbaumCKrause-SteinraufHBeckerDGitelmanS 2009 Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. The New England journal of medicine 361 2143 2152
5. SilveiraPGreyS 2006 B cells in the spotlight: innocent bystanders or major players in the pathogenesis of type 1 diabetes. Trends in endocrinology and metabolism: TEM 17 128 135
6. FlesherDTSunXBehrensTGrahamRCriswellL 2010 Recent advances in the genetics of systemic lupus erythematosus. Expert review of clinical immunology 6 461 479
7. MartinSWolf-EichbaumDDuinkerkenGScherbaumWKolbH 2001 Development of Type 1 Diabetes despite Severe Hereditary B-Cell Deficiency. New England Journal of Medicine 345 1036 1040
8. PetersenJMarshallMBækkeskovSHejnæsKHøier-MadsenM 1993 Transfer of Type 1 (insulin-dependent) diabetes mellitus associated autoimmunity to mice with severe combined immunodeficiency (SCID). Diabetologia 36 510 515
9. MillsDMCambierJC 2003 B lymphocyte activation during cognate interactions with CD4+ T lymphocytes: molecular dynamics and immunologic consequences. Seminars in immunology 15 325 329
10. WilliamsAJAitkenRJChandlerMAGillespieKMLampasonaV 2008 Autoantibodies to islet antigen-2 are associated with HLA-DRB1*07 and DRB1*09 haplotypes as well as DRB1*04 at onset of type 1 diabetes: the possible role of HLA-DQA in autoimmunity to IA-2. Diabetologia 51 1444 1448
11. GullstrandCWahlbergJIlonenJVaaralaOLudvigssonJ 2008 Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study. Pediatric Diabetes 9 182 190
12. MariottiSCaturegliPPiccoloPBarbesinoGPincheraA 1990 Antithyroid peroxidase autoantibodies in thyroid diseases. The Journal of clinical endocrinology and metabolism 71 661 669
13. JeffriesGHSleisengerMH 1965 Studies of parietal cell antibody in pernicious anemia. The Journal of clinical investigation 44 2021 2028
14. WangXJiaSGeoffreyRAlemzadehRGhoshS 2008 Identification of a molecular signature in human type 1 diabetes mellitus using serum and functional genomics. Journal of immunology (Baltimore, Md : 1950) 180 1929 1937
15. HollowellJStaehlingNFlandersDHannonHGunterE 2002 Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). The Journal of clinical endocrinology and metabolism 87 489 499
16. HowsonDungerNutlandStevensWicker 2007 A type 1 diabetes subgroup with a female bias is characterised by failure in tolerance to thyroid peroxidase at an early age and a strong association with the cytotoxic T-lymphocyte-associated antigen-4 gene. Diabetologia 50 741 746
17. WarnckeKFrohlich-ReitererEThonAHoferSWiemannD 2010 Polyendocrinopathy in Children, Adolescents, and Young Adults With Type 1 Diabetes. Diabetes Care 33 2010 2012
18. KochiYYamadaRSuzukiAHarleyJShirasawaS 2005 A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. Nature Genetics 37 478 485
19. Wellcome Trust Case Control Consortium 2007 Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nature Genetics 39 1329 1337
20. PlagnolVSmythDJToddJAClaytonDG 2008 Statistical independence of the colocalized association signals for type 1 diabetes and RPS26 gene expression on chromosome 12q13. Biostatistics 10 327 334
21. ParéGChasmanDIKelloggMZeeRYRifaiN 2008 Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women. PLoS Genet 4 e1000118 doi:10.1371/journal.pgen.1000118
22. PatersonALopes-VirellaMWaggottDBorightAHosseiniM 2009 Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin. Arteriosclerosis, thrombosis, and vascular biology 29 1958 1967
23. EdgrenGHjalgrimHRostgaardKNordaRWikmanA 2010 Risk of Gastric Cancer and Peptic Ulcers in Relation to ABO Blood Type: A Cohort Study. American Journal of Epidemiology 172 1280 1285
24. AmundadottirLKraftPStolzenberg-SolomonRFuchsCPetersenG 2009 Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nature Genetics 41 986 990
25. FrankeAMcGovernDBarrettJWangKRadford-SmithG 2010 Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nature Genetics 42 1118 1125
26. McGovernDJonesMTaylorKMarcianteKYanX 2010 Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease. Human Molecular Genetics 19 3468 3476
27. BarrettJClaytonDConcannonPAkolkarBCooperJ 2009 Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genetics 41 703 707
28. BenjaminiYHochbergY 1995 Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society Series B (Methodological) 57 289 300
29. MaziarzMJanerMRoachJCHagopianWPalmerJP 2010 The association between the PTPN22 1858C>T variant and type 1 diabetes depends on HLA risk and GAD65 autoantibodies. Genes and Immunity 11 406 415
30. ZhernakovaAvan DiemenCWijmengaC 2009 Detecting shared pathogenesis from the shared genetics of immune-related diseases. Nature Review Genetics 10 43 55
31. GatevaVSandlingJHomGTaylorKChungS 2009 A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nature Genetics 41 1228 1233
32. Special Edition on Lupus Genetics 2002 Genes and Immunity 3
33. DuboisPTrynkaGFrankeLHuntKRomanosJ 2010 Multiple common variants for celiac disease influencing immune gene expression. Nature Genetics 42 295 302
34. VandewalleCLFalorniALernmarkAGoubertPDorchyH 1997 Associations of GAD65 - and IA-2 - autoantibodies with genetic risk markers in new-onset IDDM patients and their siblings. The Belgian Diabetes Registry. Diabetes care 20 1547 1552
35. GrahamJHagopianWKockumILiLSSanjeeviC 2002 Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes. Diabetes 51 1346 1355
36. QuH-QPolychronakosC 2009 The effect of the MHC locus on autoantibodies in type 1 diabetes. Journal of medical genetics
37. KnipMKukkoMKulmalaPVeijolaRSimellO 2002 Humoral beta-cell autoimmunity in relation to HLA-defined disease susceptibility in preclinical and clinical type 1 diabetes. American journal of medical genetics 115 48 54
38. KordonouriOHartmannRCharpentierNKnipMDanneT 2010 Genetic risk markers related to diabetes-associated autoantibodies in young patients with type 1 diabetes in berlin, Germany. Experimental and clinical endocrinology & diabetes 118 245 249
39. KondrashovaAViskariHHaapalaA-MSeiskariTKulmalaP 2008 Serological evidence of thyroid autoimmunity among schoolchildren in two different socioeconomic environments. The Journal of clinical endocrinology and metabolism 93 729 734
40. LindbergBCarlssonAEricssonUBKockumILernmarkA 1999 Prevalence of beta-cell and thyroid autoantibody positivity in schoolchildren during three-year follow-up. Autoimmunity 31 175 185
41. RoseNMacKayI 1998 The Autoimmune Diseases, third edition Academic Press
42. RoepBODuinkerkenGSchreuderGMKolbHde VriesRR 1996 HLA-associated inverse correlation between T cell and antibody responsiveness to islet autoantigen in recent-onset insulin-dependent diabetes mellitus. European journal of immunology 26 1285 1289
43. SwainsonLMoldJBajpaiUMcCuneJ 2010 Expression of the Autoimmune Susceptibility Gene FcRL3 on Human Regulatory T Cells Is Associated with Dysfunction and High Levels of Programmed Cell Death-1. The Journal of Immunology 184 3639 3647
44. LindénSMahdaviJSemino-MoraCOlsenCCarlstedtI 2008 Role of ABO Secretor Status in Mucosal Innate Immunity and H. pylori Infection. PLoS Path 4 e2 doi:10.1371/journal.ppat.0040002
45. UmlauftFKeeffeEBOffnerFWeissGFeichtingerH 1996 Helicobacter pylori infection and blood group antigens: lack of clinical association. The American journal of gastroenterology 91 2135 2138
46. AlkoutABlackwellCWeirD 2000 Increased Inflammatory Responses of Persons of Blood Group O to Helicobacter pylori. Journal of Infectious Diseases 181 1364 1369
47. RobertsJA 1957 Blood groups and susceptibility to disease: a review. British journal of preventive & social medicine 11 107 125
48. CallenderSLangmanMJMacleodINMosbechJNielsenKR 1971 ABO blood groups in patients with gastric carcinoma associated with pernicious anaemia. Gut 12 465 467
49. HoskinsLCLouxHABrittenAZamcheckN 1965 Distribution of ABO blood groups in patients with pernicious anemia, gastric carcinoma and gastric carcinoma associated with pernicious anemia. The New England journal of medicine 273 633 637
50. MaierLAndersonDSeversonCBaecher-AllanCHealyB 2009 Soluble IL-2RA levels in multiple sclerosis subjects and the effect of soluble IL-2RA on immune responses. Journal of immunology 182 1541 1547
51. MarciulionyteDWilliamsAJBingleyPJUrbonaiteBGaleEA 2001 A comparison of the prevalence of islet autoantibodies in children from two countries with differing incidence of diabetes. Diabetologia 44 16 21
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