CDS1 and promoter single nucleotide polymorphisms of the CTLA-4 gene in human myasthenia gravis

The cytotoxic T lymphocyte associated protein 4 (CTLA-4) gene (Ctla-4) is a candidate gene for autoimmune disease. We here report results of two single nucleotide polymorphisms (SNPs) in the Ctla-4, a +49 A/G SNP in CDS1 and a C/T promoter SNP at position −318. There were no differences in these two SNPs between patients and healthy individuals. The frequency of allele G and genotype G/G at position +49 in CDS1 was increased in patients with thymoma when compared with patients with normal and hyperplastic thymic histopathology. Patients with the G/G genotype had signs of immune activation manifested as higher levels of serum IL-1β and higher percentage of CD28+ T lymphocytes. There was a strong linkage between the 86 bp allele in the 3′-UTR and the A+49 allele in CDS1. Our results suggest that the SNP at position +49 in CDS1 might be associated with the manifestations of MG.