Genetic determinants of type 1 diabetes across populations.
T1D results from autoimmune-mediated destruction of the pancreatic beta cells, a process that is conditioned by multiple genes and environmental factors. The main genetic determinants map to the major histocompatibility complex (MHC), and in particular DR and DQ, although, genes outside the MHC contribute, including the insulin gene, PTPN22, and CTLA-4. There are remarkable differences in genetic susceptibility to T1D between populations. We believe this variation reflects differing frequencies of diabetes causative and protective alleles and haplotypes, and thus remains a major genetic influence linked to the MHC region not accounted for by DR and DQ alleles. In this article, we discuss global variations in genetic susceptibility to T1D in view of current genetic understanding.
Jahromi
Mohamed M
MM
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, PO Box 6511, Aurora, CO 80010, USA.
Eisenbarth
George S
GS
D015703:Antigens, CD / Q000235:genetics; D000943:Antigens, Differentiation / Q000235:genetics; D060908:CTLA-4 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D014644:Genetic Variation; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics; D044382:Population Groups / Q000235:genetics*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007328:Insulin; C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases