An association between the CTLA4 exon 1 polymorphism and early rheumatoid arthritis with autoimmune endocrinopathies

Rheumatology (Oxford). 2002 Feb;41(2):180-3. doi: 10.1093/rheumatology/41.2.180.


Objective: To examine the allelic association of the single nucleotide polymorphism (CTLA4A/G) in exon 1 of the cytotoxic T lymphocyte antigen-4 (CTLA4) gene with early rheumatoid arthritis (RA).

Methods: One hundred and twenty-three unrelated white probands with early RA from the north-east of England and 349 local ethnically matched controls were studied. The CTLA4A/G polymorphism was genotyped with a polymerase chain reaction (PCR) method and digestion with the restriction enzyme Bst71I. Probands were also screened by allele-specific PCR for alleles HLA DRB1*01 and DRB1*04.

Results: The frequency of the G allele at CTLA4A/G was significantly increased in probands with early RA compared with controls [43 vs 36%; P=0.028, odds ratio (OR) 1.35, 95% confidence interval (CI) 1.01-1.82]. Most of this increased frequency was attributable to RA individuals with coexisting autoimmune thyroid disease or type 1 diabetes (58 vs 36% in controls; P=0.005, OR 2.50, CI 1.29-4.84). The frequency of the G allele in RA patients without autoimmune endocrinopathy was 40%, which was not significantly different from that in controls (P=0.140).

Conclusion: The association between the CTLA4 G allele and early RA is largely explained by individuals with RA who have coexisting autoimmune endocrinopathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Antigens, CD
  • Antigens, Differentiation / genetics*
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • CTLA-4 Antigen
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Exons
  • Female
  • Genotype
  • Humans
  • Immunoconjugates*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Radiography
  • Thyroiditis, Autoimmune / genetics*
  • Thyroiditis, Autoimmune / immunology


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoconjugates
  • Abatacept