The CTLA-4 gene is associated with multiple sclerosis

J Neuroimmunol. 1999 Jun 1;97(1-2):182-90. doi: 10.1016/s0165-5728(99)00072-7.

Abstract

We have investigated whether three intragenic polymorphisms of the CTLA-4 gene, a C/T base exchange in the promoter (p.-318), an A/G substitution in exon 1 (p.49) and a dinucleotide repeat polymorphism in exon 4 (p.642), were associated with genetic susceptibility to multiple sclerosis (MS). We observed a significant association (p < 0.05) for homozygosity for the G49 allele in a case-control analysis of 378 MS patients and 237 controls, and a transmission disequilibrium (p < 0.02) for the G49 allele in 31 MS families. This was further corroborated by evidence for linkage by the affected pedigree member (APM) analysis (p < 0.0002) and a transmission distortion (p < 0.05) of the exon 4(642) polymorphism. Sequencing of the promoter, the first and second exons and the parts of the first intron revealed no further polymorphisms. Our results suggest that a dysregulation of CTLA-4-driven downregulation of T-cell activation could be involved in the pathogenesis of MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Antigens, CD
  • Antigens, Differentiation / genetics*
  • Antigens, Differentiation / immunology*
  • CTLA-4 Antigen
  • Chromosomes, Human, Pair 2*
  • DNA Primers
  • DNA, Satellite / analysis
  • Exons
  • Family Health
  • Female
  • Genetic Linkage
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-DR Antigens / analysis
  • HLA-DR Antigens / immunology
  • Humans
  • Immunoconjugates*
  • Immunosuppressive Agents / immunology*
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Phenotype
  • Polymorphism, Genetic
  • Promoter Regions, Genetic / immunology
  • Sequence Analysis, DNA
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • DNA Primers
  • DNA, Satellite
  • Genetic Markers
  • HLA-DR Antigens
  • Immunoconjugates
  • Immunosuppressive Agents
  • Abatacept

Associated data

  • GENBANK/M37243
  • GENBANK/M74363