TY - JOUR
T1 - HLA and autoimmune diseases
T2 - Type 1 diabetes (T1D) as an example
AU - Gorodezky, Clara
AU - Alaez, Carmen
AU - Murguía, Andrea
AU - Rodríguez, Araceli
AU - Balladares, Sandra
AU - Vazquez, Miriam
AU - Flores, Hilario
AU - Robles, Carlos
N1 - Funding Information:
This study was done partly with the support of The Royal Academy of Physical, Natural and Exact Sciences of Spain, Madrid 1994.
PY - 2006/3
Y1 - 2006/3
N2 - Autoimmune diseases need to be considered at a genetic and mechanistic level. T1D is an autoimmune, chronic, multifactorial and polygenic disease characterized by the destruction of the pancreatic β-cells associated with long term dysfunction of several organs and tissues. Mechanisms of susceptibility include epi-genetic and post-transcriptional effects that regulate transmission and expression of the inherited genes. The HLA complex, constitutes the most relevant region contributing 50% of the inherited risk for T1D. An additional 17 genes with variable but small effects have been described. In non-Caucasians, the presence of E-DRβ1-74 and/or D-DRβ1-57 are relevant in predisposition. The "Diabetogenic haplotypes" in Mexicans were DRB1*0301-DQA1*0501-DQB1*0201 (OR = 21.4); DRB1*0405-DQA1-*0301-DQB1*0302 (OR = 44.5) and the same DQA1/DQB1 with DRB1*0404/*0401 conferring lower risk, increasing (OR = 61.3) with an early age at onset and a heterozygote DR3/DR4 genotype. In most populations, the absence of D-57 and the presence of R-52 are important to the susceptibility, but in Hispanics, all DR4s (including the protective DRB1*0403/*0407/*0411) are in linkage disequilibrium with DQA1/DQB1 susceptibility alleles. Thus, susceptibility alleles in Latin American Mestizos are of Mediterranean ancestry whereas protective alleles are of Amerindian origin. In this review, we discuss the complexity of T1D and some aspects of prevention/intervention based on immunogenetics.
AB - Autoimmune diseases need to be considered at a genetic and mechanistic level. T1D is an autoimmune, chronic, multifactorial and polygenic disease characterized by the destruction of the pancreatic β-cells associated with long term dysfunction of several organs and tissues. Mechanisms of susceptibility include epi-genetic and post-transcriptional effects that regulate transmission and expression of the inherited genes. The HLA complex, constitutes the most relevant region contributing 50% of the inherited risk for T1D. An additional 17 genes with variable but small effects have been described. In non-Caucasians, the presence of E-DRβ1-74 and/or D-DRβ1-57 are relevant in predisposition. The "Diabetogenic haplotypes" in Mexicans were DRB1*0301-DQA1*0501-DQB1*0201 (OR = 21.4); DRB1*0405-DQA1-*0301-DQB1*0302 (OR = 44.5) and the same DQA1/DQB1 with DRB1*0404/*0401 conferring lower risk, increasing (OR = 61.3) with an early age at onset and a heterozygote DR3/DR4 genotype. In most populations, the absence of D-57 and the presence of R-52 are important to the susceptibility, but in Hispanics, all DR4s (including the protective DRB1*0403/*0407/*0411) are in linkage disequilibrium with DQA1/DQB1 susceptibility alleles. Thus, susceptibility alleles in Latin American Mestizos are of Mediterranean ancestry whereas protective alleles are of Amerindian origin. In this review, we discuss the complexity of T1D and some aspects of prevention/intervention based on immunogenetics.
KW - Autoimmunity
KW - Genetics
KW - MHC
KW - Susceptibility/protection
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=32544460844&partnerID=8YFLogxK
U2 - 10.1016/j.autrev.2005.06.002
DO - 10.1016/j.autrev.2005.06.002
M3 - Artículo
C2 - 16483918
AN - SCOPUS:32544460844
SN - 1568-9972
VL - 5
SP - 187
EP - 194
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
IS - 3
ER -