OBJECTIVE: To analyze the association of Wegener's granulomatosis (WG) with 2 single nucleotide polymorphisms (SNP), a +49 A/G polymorphism in coding sequence (CDS) 1 and a C/T base exchange in the promoter region at position -318. METHODS: Restriction enzyme digestion of PCR amplified genomic DNA was used to analyze the CTLA-4 SNP in 32 patients with WG and 100-122 ethnically matched healthy controls. RESULTS: Patients were more often heterozygous for C/T in the promoter region (31% of the patients vs 14% of controls; p < 0.05). Homozygosity for C was less frequent in patients (69% of patients vs 86% of controls; p < 0.05). There was no association with the A/G SNP in CDS 1. There was a linkage disequilibrium between allele A of CDS 1 and the shortest allele, 86 bp, in the (AT)n of the 3' untranslated region in controls but not in patients. CONCLUSION: The CTLA-4 SNP in the promoter region at position -318 is associated with WG. The loss of linkage disequilibrium between allele A of CDS 1 and the short 86 bp in the (AT)n in patients indicates that the promoter SNP and the (AT)n polymorphism are independent genetic risk factors.
OBJECTIVE: To analyze the association of Wegener's granulomatosis (WG) with 2 single nucleotide polymorphisms (SNP), a +49 A/G polymorphism in coding sequence (CDS) 1 and a C/T base exchange in the promoter region at position -318. METHODS: Restriction enzyme digestion of PCR amplified genomic DNA was used to analyze the CTLA-4 SNP in 32 patients with WG and 100-122 ethnically matched healthy controls. RESULTS:Patients were more often heterozygous for C/T in the promoter region (31% of the patients vs 14% of controls; p < 0.05). Homozygosity for C was less frequent in patients (69% of patients vs 86% of controls; p < 0.05). There was no association with the A/G SNP in CDS 1. There was a linkage disequilibrium between allele A of CDS 1 and the shortest allele, 86 bp, in the (AT)n of the 3' untranslated region in controls but not in patients. CONCLUSION: The CTLA-4 SNP in the promoter region at position -318 is associated with WG. The loss of linkage disequilibrium between allele A of CDS 1 and the short 86 bp in the (AT)n in patients indicates that the promoter SNP and the (AT)n polymorphism are independent genetic risk factors.
Authors: Sharon A Chung; Gang Xie; Delnaz Roshandel; Richard Sherva; Jeffrey C Edberg; Megan Kravitz; Paul F Dellaripa; Gary S Hoffman; Alfred D Mahr; Philip Seo; Ulrich Specks; Robert F Spiera; E William St Clair; John H Stone; Robert M Plenge; Katherine A Siminovitch; Peter A Merkel; Paul A Monach Journal: Arthritis Rheum Date: 2012-10
Authors: Matthew D Morgan; Clara J Day; Karen P Piper; Naeem Khan; Lorraine Harper; Paul A Moss; Caroline O S Savage Journal: Immunology Date: 2010-01-27 Impact factor: 7.397
Authors: Gang Xie; Delnaz Roshandel; Richard Sherva; Paul A Monach; Emily Yue Lu; Tabitha Kung; Keisha Carrington; Steven S Zhang; Sara L Pulit; Stephan Ripke; Simon Carette; Paul F Dellaripa; Jeffrey C Edberg; Gary S Hoffman; Nader Khalidi; Carol A Langford; Alfred D Mahr; E William St Clair; Philip Seo; Ulrich Specks; Robert F Spiera; John H Stone; Steven R Ytterberg; Soumya Raychaudhuri; Paul I W de Bakker; Lindsay A Farrer; Christopher I Amos; Peter A Merkel; Katherine A Siminovitch Journal: Arthritis Rheum Date: 2013-09