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Coding Sequence 1 and Promoter Single Nucleotide Polymorphisms in the CTLA-4 Gene in Wegener's Granulomatosis
RICARDO GISCOMBE, XIONGBIAO WANG, DEREN HUANG, and ANN KARI LEFVERT
ABSTRACT.
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. (J Rheumatol 2002;29:950-3) Key Indexing Terms:
WEGENER'S GRANULOMATOSIS
From the Immunological Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Supported by grants from the Swedish Heart-Lung Foundation, the King Gustaf V 80 Years Foundation, the Börje Dahlin Foundation, the Swedish Rheumatism Association, and the Swedish Medical Research Council. R. Giscombe, PhD; X.B. Wang, MD, PhD; D.R. Huang, MD, PhD; A.K. Lefvert, Professor. Address reprint requests to Professor A.K. Lefvert, Immunological Research Unit, CMM, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail: Ann.Kari.Lefvert@cmm.ki.se Submitted May 23, 2001; revision accepted November 6, 2001. |