No association of the codon 55 methionine to valine polymorphism in the SUMO4 gene with Graves' disease

Clin Endocrinol (Oxf). 2005 Mar;62(3):362-5. doi: 10.1111/j.1365-2265.2005.02224.x.


Objective: A functional polymorphism at codon 55 of the small ubiquitin-like modifier-4 (SUMO4) gene (methionine to valine; M55V) has recently been associated with type 1 diabetes mellitus (T1D). We aimed to establish whether this locus also contributes towards the genetic susceptibility to Graves' disease (GD) and autoimmune Addison's disease.

Design: A case-control analysis was performed using genomic DNA samples from 595 unrelated white GD subjects, 104 white autoimmune Addison's disease subjects and 467 healthy white control subjects. The SUMO4 M55V single nucleotide polymorphism (SNP) was genotyped using polymerase chain reaction (PCR) amplification followed by digestion with the restriction enzyme MseI.

Results: There was no association of the SUMO4 M55V alleles with either GD, thyroid-associated orbitopathy or autoimmune Addison's disease when compared to controls; P = 0.28, 0.46 and 0.91, respectively, by chi2 testing.

Conclusion: We cannot confirm a generalized role for SUMO4 in autoimmune endocrinopathy. The SUMO4 codon 55 methionine to valine polymorphism may be exclusively associated with susceptibility to T1D, or the effect of the locus in GD and Addison's disease may be much less than that found in T1D patients.

MeSH terms

  • Addison Disease / genetics
  • Case-Control Studies
  • Codon / genetics
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Graves Disease / genetics*
  • Humans
  • Methionine / genetics
  • Polymorphism, Single Nucleotide*
  • Small Ubiquitin-Related Modifier Proteins / genetics*
  • Valine / genetics


  • Codon
  • SUMO4 protein, human
  • Small Ubiquitin-Related Modifier Proteins
  • Methionine
  • Valine