Coding sequence 1 and promoter single nucleotide polymorphisms in the CTLA-4 gene in Wegener's granulomatosis

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 link-age 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 link-age 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.