Association between Synapsin III gene promoter polymorphisms and multiple sclerosis

J Neurol. 2004 Feb;251(2):165-70. doi: 10.1007/s00415-004-0293-7.

Abstract

Although multiple sclerosis (MS) is considered to be an inflammatory demyelinating disease, increasing evidence indicates that it is also an axonal pathology; indeed, studies of experimental allergic encephalitis showed that several neuronal proteins such as synapsins take part in the pathogenesis of the axonal dysfunction. Synapsins are a family of abundant neuron-specific phosphoproteins with crucial roles in synaptogenesis and neuronal plasticity. Distinct genes encode the three different isolated proteins (I, II and III); of interest, the gene of synapsin III (SYN3) is located in the chromosome 22q12-q13, a locus close to one of the candidate susceptibility regions (22q13.1) for MS. In the present study we selected two polymorphisms (g.-631C > G and g.-196A > G) within the SYN3 5'-promoter region because of the protein's role and genetic location; we analysed the allele and genotype distributions of these polymorphisms in a selected MS population of southern Italy. An inverse association between MS and the g-631C > G polymorphism was found; indeed, the two polymorphisms were in almost complete linkage disequilibrium and the haplotype analysis showed that the C631/A196 haplotype seemed to confer a significant protection against MS.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Axons / metabolism
  • Axons / pathology
  • Child
  • Chromosomes, Human, Pair 22 / genetics
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genotype
  • Haplotypes
  • Humans
  • Italy
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / physiopathology
  • Mutation / genetics*
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neuropeptides / genetics*
  • Phosphoproteins / genetics*
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic / genetics*
  • Synapsins

Substances

  • Neuropeptides
  • Phosphoproteins
  • SYN3 protein, human
  • Synapsins