Genetic factors in type 1 diabetes: A complex disease

Jin Xiong She

Research output: Contribution to journalReview articlepeer-review


Insulin-dependent diabetes mellitus (IDDM or type 1 diabetes) is a complex (multifactorial) disease, in which the expression of the disease phenotype is influenced by a large number of genes as well as environmental factors. Genome wide linkage analyses indicate that the most important genetic factors in IDDM are encoded in the HLA region on chromosome 6p21, which, indeed, contains multiple susceptibility genes. The HLA-DR and -DQ molecules are important genetic factors and they may confer susceptible, neutral, or protective effects on risk for IDDM. The overall risk may be determined by the counter-balancing effect of all HLA class II molecules in an individual. Therefore, HLA genotypes, instead of individual alleles, should be considered for risk prediction. A second IDDM locus has been mapped to the VNTR (variable number of tandem repeat) at the 5' end of the insulin (INS) gene on chromosome 11p15. The size and sequence of this repetitive element play a role in the regulation of INS expression in the thymus, suggesting that tolerance induction to insulin may be relevant to the pathogenesis of IDDM. Recent linkage studies also revealed 13 additional genomic regions that may contain IDDM susceptibility genes. Only four of these intervals (IDDM4 on 11q,IDDM5 on 6q25,IDDM8, and IDDM12 on 2q33) have been confirmed in multiple studies. One of the confirmed intervals (IDDM12) has been localized to a genomic region of less than 100 kb which contains the immuno-regulatory molecule CTLA4. The identified genetic factors are already useful for IDDM prediction in relatives of diabetic patients and in the general population. However, these and additional genetic markers in combination with immunological markers will provide the most specific and sensitive tests for the prediction of IDDM.

Original languageEnglish (US)
Pages (from-to)272-281
Number of pages10
JournalJournal of Clinical Ligand Assay
Issue number3
StatePublished - Sep 1998
Externally publishedYes


  • Association analysis
  • Autoimmune diseases
  • CTLA4
  • Disease risk
  • HLA
  • IDDM
  • Insulin
  • Linkage analysis
  • Linkage disequilibrium
  • Type 1 diabetes
  • VNTR

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical


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