CONTEXT: A recent large-scale analysis of nonsynonymous coding polymorphisms showed strong evidence that an alanine to threonine amino acid change at codon 946 of the interferon-induced helicase (IFIH1) gene (SNP ID rs1990760) was associated with type 1 diabetes. Previous investigations have also demonstrated that an intronic polymorphism (termed PD1.3; SNP ID rs11568821) in the programmed cell death (PDCD1) gene was associated with systemic lupus erythematosus and rheumatoid arthritis. OBJECTIVE: We sought to replicate these genetic associations in Graves' disease and autoimmune Addison's disease patient cohorts. PATIENTS AND METHODS: A total of 602 Graves' disease subjects, 214 Addison's disease subjects, and 446 healthy controls were genotyped for the IFIH1 and PDCD1 single-nucleotide polymorphisms using mass spectrometer analysis of primer extension products (Sequenom). RESULTS: The alanine-carrying allele at the IFIH1 codon 946 polymorphism was present in 796 of 1204 (66%) Graves' disease patient alleles compared with 508 of 892 (57%) control subject alleles [odds ratio 1.47 (5-95% confidence interval, 1.23-1.76); P = 1.9 x 10(-5)]. In contrast, there was no association of alleles at this marker in autoimmune Addison's disease. Neither was there evidence for association in either patient cohort at the PD1.3 polymorphism. CONCLUSIONS: We confirm a significant contribution of the Ala946Thr IFIH1 polymorphism to organ-specific autoimmune diseases, extending the range of conditions associated with this variant to include Graves' disease. This polymorphism may also contribute to several other autoimmune disorders.
CONTEXT: A recent large-scale analysis of nonsynonymous coding polymorphisms showed strong evidence that an alanine to threonine amino acid change at codon 946 of the interferon-induced helicase (IFIH1) gene (SNP ID rs1990760) was associated with type 1 diabetes. Previous investigations have also demonstrated that an intronic polymorphism (termed PD1.3; SNP ID rs11568821) in the programmed cell death (PDCD1) gene was associated with systemic lupus erythematosus and rheumatoid arthritis. OBJECTIVE: We sought to replicate these genetic associations in Graves' disease and autoimmune Addison's disease patient cohorts. PATIENTS AND METHODS: A total of 602 Graves' disease subjects, 214 Addison's disease subjects, and 446 healthy controls were genotyped for the IFIH1 and PDCD1 single-nucleotide polymorphisms using mass spectrometer analysis of primer extension products (Sequenom). RESULTS: The alanine-carrying allele at the IFIH1 codon 946 polymorphism was present in 796 of 1204 (66%) Graves' disease patient alleles compared with 508 of 892 (57%) control subject alleles [odds ratio 1.47 (5-95% confidence interval, 1.23-1.76); P = 1.9 x 10(-5)]. In contrast, there was no association of alleles at this marker in autoimmune Addison's disease. Neither was there evidence for association in either patient cohort at the PD1.3 polymorphism. CONCLUSIONS: We confirm a significant contribution of the Ala946Thr IFIH1 polymorphism to organ-specific autoimmune diseases, extending the range of conditions associated with this variant to include Graves' disease. This polymorphism may also contribute to several other autoimmune disorders.
Authors: Hironori Ueda; Joanna M M Howson; Laura Esposito; Joanne Heward; Hywel Snook; Giselle Chamberlain; Daniel B Rainbow; Kara M D Hunter; Annabel N Smith; Gianfranco Di Genova; Mathias H Herr; Ingrid Dahlman; Felicity Payne; Deborah Smyth; Christopher Lowe; Rebecca C J Twells; Sarah Howlett; Barry Healy; Sarah Nutland; Helen E Rance; Vin Everett; Luc J Smink; Alex C Lam; Heather J Cordell; Neil M Walker; Cristina Bordin; John Hulme; Costantino Motzo; Francesco Cucca; J Fred Hess; Michael L Metzker; Jane Rogers; Simon Gregory; Amit Allahabadia; Ratnasingam Nithiyananthan; Eva Tuomilehto-Wolf; Jaakko Tuomilehto; Polly Bingley; Kathleen M Gillespie; Dag E Undlien; Kjersti S Rønningen; Cristian Guja; Constantin Ionescu-Tîrgovişte; David A Savage; A Peter Maxwell; Dennis J Carson; Chris C Patterson; Jayne A Franklyn; David G Clayton; Laurence B Peterson; Linda S Wicker; John A Todd; Stephen C L Gough Journal: Nature Date: 2003-04-30 Impact factor: 49.962
Authors: Ludmila Prokunina; Casimiro Castillejo-López; Fredrik Oberg; Iva Gunnarsson; Louise Berg; Veronica Magnusson; Anthony J Brookes; Dmitry Tentler; Helga Kristjansdóttir; Gerdur Gröndal; Anne Isine Bolstad; Elisabet Svenungsson; Ingrid Lundberg; Gunnar Sturfelt; Andreas Jönssen; Lennart Truedsson; Guadalupe Lima; Jorge Alcocer-Varela; Roland Jonsson; Ulf B Gyllensten; John B Harley; Donato Alarcón-Segovia; Kristján Steinsson; Marta E Alarcón-Riquelme Journal: Nat Genet Date: 2002-10-28 Impact factor: 38.330
Authors: Bryan M Dechairo; Delilah Zabaneh; Joanne Collins; Oliver Brand; Gary J Dawson; Angie P Green; Ian Mackay; Jayne A Franklyn; John M Connell; John A H Wass; Wilmar M Wiersinga; Laszlo Hegedus; Thomas Brix; Bruce G Robinson; Penny J Hunt; Anthony P Weetman; Alisoun H Carey; Stephen C Gough Journal: Eur J Hum Genet Date: 2005-11 Impact factor: 4.246
Authors: S H Pearce; T Cheetham; H Imrie; B Vaidya; N D Barnes; R W Bilous; D Carr; K Meeran; N J Shaw; C S Smith; A D Toft; G Williams; P Kendall-Taylor Journal: Am J Hum Genet Date: 1998-12 Impact factor: 11.025
Authors: Catherine J Owen; Hannah Kelly; James A Eden; Marilyn E Merriman; Simon H S Pearce; Tony R Merriman Journal: J Clin Endocrinol Metab Date: 2007-01-02 Impact factor: 5.958
Authors: John T Crowl; Elizabeth E Gray; Kathleen Pestal; Hannah E Volkman; Daniel B Stetson Journal: Annu Rev Immunol Date: 2017-01-30 Impact factor: 28.527
Authors: Siyang Liu; Hongjie Wang; Yulan Jin; Robert Podolsky; M V Prasad Linga Reddy; Jennifer Pedersen; Bruce Bode; John Reed; Dennis Steed; Steve Anderson; Ping Yang; Andy Muir; Leigh Steed; Diane Hopkins; Yihua Huang; Sharad Purohit; Cong-Yi Wang; Andrea K Steck; Annalisa Montemari; George Eisenbarth; Marian Rewers; Jin-Xiong She Journal: Hum Mol Genet Date: 2008-10-16 Impact factor: 6.150
Authors: Donna L Thibault Flesher; Xin Sun; Timothy W Behrens; Robert R Graham; Lindsey A Criswell Journal: Expert Rev Clin Immunol Date: 2010-05 Impact factor: 4.473
Authors: Vesela Gateva; Johanna K Sandling; Geoff Hom; Kimberly E Taylor; Sharon A Chung; Xin Sun; Ward Ortmann; Roman Kosoy; Ricardo C Ferreira; Gunnel Nordmark; Iva Gunnarsson; Elisabet Svenungsson; Leonid Padyukov; Gunnar Sturfelt; Andreas Jönsen; Anders A Bengtsson; Solbritt Rantapää-Dahlqvist; Emily C Baechler; Elizabeth E Brown; Graciela S Alarcón; Jeffrey C Edberg; Rosalind Ramsey-Goldman; Gerald McGwin; John D Reveille; Luis M Vilá; Robert P Kimberly; Susan Manzi; Michelle A Petri; Annette Lee; Peter K Gregersen; Michael F Seldin; Lars Rönnblom; Lindsey A Criswell; Ann-Christine Syvänen; Timothy W Behrens; Robert R Graham Journal: Nat Genet Date: 2009-10-18 Impact factor: 38.330
Authors: Marissa Penna-Martinez; Elizabeth Ramos-Lopez; Inka Robbers; Heinrich Kahles; Stefanie Hahner; Holger Willenberg; Nicole Reisch; Christian Seidl; Maria Segni; Klaus Badenhoop Journal: BMC Med Genet Date: 2009-12-04 Impact factor: 2.103