CTLA4 CODON-17 DIMORPHISM IN PATIENTS WITH RHEUMATOID-ARTHRITIS

The genetic susceptibility to rheumatoid arthritis is conferred by gen es in the human leukocyte antigen (HLA) region an chromosome 6, but ad ditional genes may be involved to determine disease susceptibility. We have studied the distribution of the CTLA4 exon 1 polymorphism (49 A/ G) in rheumatoid arthritis. This dimorphism at codon 17 results in an amino acid exchange (Thr/Ala) in the leader peptide of the expressed p rotein and was analyzed by PCR, SSCP and RFLP in 255 Caucasian rheumat oid arthritis patients and 456 controls, Rheumatoid arthritis patients mere characterized by a decreased frequency of homozygotes for the Th r-17 substitution (32% versus 39%) and an overrepresentation of patien ts heterozygous for the Thr/Ala substitution (54% versus 46%). Gene fr equencies for the Ala/Thr substitution differed only marginally from c ontrols. In contrast analyses, of the CTLA4 exon 1 polymorphism with r espect to HLA-DRB104 revealed significantly more patients with fila i n the homozygous (19% versus 15% controls) or heterozygous state (54% versus 39% controls) and less homozygous for Thr (27% versus 46% contr ols), with a particular increase of Ala/Ala genotypes among rheumatoid arthritis patients carrying the HLA-DRB10401 subtype. Among HL.4-DRB 104 negative rheumatoid arthritis patients, we observed no difference between the allele frequencies of the Ala-17 or Thr-17 substitution.