[MHC-dependent molecular mechanisms of susceptibility and protection in type I diabetes in Mexicans]

MHC class II genes play an important role in the autoimmune destruction of the pancreatic b-cell occurring in IDDM. The genetic pattern of the disease was investigated in Mexican Mestizos. The serological findings of HLA antigens showed a significant association of DR3, DR4, DQ2 and DQ8 and a protective effect of DR11, DR15, DQ5, DQ6 and DQ7. With these results, DNA analysis of HLA-DRB1, B3, B4, DQA1, DQB1, DPA1, DPB1 genes was performed using PCR with allele specific oligotyping. Among the patients, 92.78 carry DQA1 alleles that have ARG in position 52 of DQa chain, and 78.2% are ASP- in DQ5-57. The RR for homozygotes is 32.8 and 5.6, respectively. The main haplotype involved is DRB1*0405, DQA1*0301, DQB1*0302. Thus, DQa and DQb form a relevant recognition site for the "diabetogenic peptidett which induces the autoimmune destruction. Positions 57 and 74 of DRB1 locus contribute highly to the expression and severity of IDDM in Mestizos and other ethnic groups, but not in Caucasians or Blacks.