Polymorphisms in the cathepsin L2 (CTSL2) gene show association with type 1 diabetes and early-onset myasthenia gravis

Hum Immunol. 2007 Sep;68(9):748-55. doi: 10.1016/j.humimm.2007.05.009. Epub 2007 Jun 28.


Type 1 diabetes (T1D) is an autoimmune disease characterized by loss of beta cells in the pancreas. The CTSL2 gene encodes the cysteine protease cathepsin V involved in antigen presentation in human cortical thymic epithelial cells, and involvement of the protease in autoimmunity has been suggested. This study aimed to evaluate CTSL2 as a candidate gene for T1D, and test whether the gene predisposes more generally to autoimmune diseases. Four polymorphisms aiming at tagging the CTSL2 locus were genotyped in 421 T1D families, and subsequently in 861 rheumatoid arthritis patients, 530 juvenile idiopathic arthritis patients, and 559 controls of Norwegian origin. Additionally, DNA from 83 German myasthenia gravis (MG) patients and 244 controls were investigated. A polymorphism, rs16919034, situated downstream of CTSL2 was associated with T1D (60.8%T, p = 0.008; p(c) = 0.03). An association with early-onset MG (45% in cases vs 36.6% in controls; p = 0.03) was observed for another polymorphism (rs4361859) situated upstream of the gene, but within the same linkage disequilibrium block. No association was observed in rheumatoid arthritis or juvenile idiopathic arthritis. Our findings suggest that the CTSL2 gene is associated with T1D and with early-onset MG.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Cathepsin L
  • Cathepsins / genetics*
  • Child
  • Child, Preschool
  • Cysteine Endopeptidases / genetics*
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Infant
  • Linkage Disequilibrium
  • Male
  • Myasthenia Gravis / epidemiology
  • Myasthenia Gravis / genetics*
  • Polymorphism, Single Nucleotide*


  • Cathepsins
  • Cysteine Endopeptidases
  • CTSL protein, human
  • Cathepsin L
  • CTSV protein, human