Chester A. Alper, M.D.
Senior Investigator, PCMM at Boston Children’s Hospital
Professor, Department of Pediatrics, Harvard Medical School
- Contact Information
- Office Phone: 617.713.8850
- Lab Phone: 617.713.8850
- Email: alp...@idi.harvard.edu
The genetics of HLA-associated disease
Larsen, C. E.; Alper, C. A.
Curr Opin Immunol (2004), Volume: 16, Issue: 5, Pages: 660-7
Type 1 diabetes mellitus (T1D) remains the most intensively studied and thus the best paradigm of major histocompatibility complex (MHC)-associated diseases. Accumulating evidence suggests that MHC susceptibility for T1D is recessive, with susceptibility alleles more common than protective alleles. Updated allele-level and nucleotide sequence analysis of MHC class II T1D susceptibility markers of conserved extended haplotypes underscore the uncertainty of the actual T1D MHC susceptibility locus. Recent studies establish that disease concordance in dizygotic twins is the same as that in siblings generally for both T1D and the MHC-associated autoimmune disease gluten-sensitive enteropathy, leaving little room for a differential environmental trigger. Epigenetic mechanisms are likely involved in many MHC-associated phenomena, including autoimmunity, and appear to be the best explanation for incomplete penetrance.