RESUMEN
OBJECTIVE: To analyze the association between human leukocyte antigen (HLA) and insulin-dependent diabetes mellitus (IDDM) in the Egyptian population for the first time and, thus, to determine the frequency of risk-associated alleles identified by a genomic HLA class II typing. Egyptians are genetically classified as North Africans and considered to be between Caucasoids and Africans (closer to Caucasoids). RESEARCH DESIGN AND METHODS: HLA class II typing was performed for 50 IDDM patients and 50 healthy control subjects by a restriction fragment-length polymorphism (RFLP) technique. The analysis of position 57 of the DQB1 molecules was conducted by polymerase chain reaction and specific sequence oligonucleotide hybridization. RESULTS: The frequency of DRB1*0301-DRB3*0201-DQA1*0501-DQB1*0201 haplotype was 43.9% in the IDDM patients and 7.1% in the control subjects (P < 0.00001), reflecting the increased prevalence of DQA1*0501 susceptibility allele coding for arginine (Arg) in position 52 and DQB1*0201 susceptibility allele non-coding aspartic acid (Asp) at position 57. Alleles DQB1*0601 and 0603, both carrying Asp at position 57 of the beta-chain, and DQA1*0103, encoding a non-Arg 52 alpha-chain, were significantly decreased among the IDDM patients. The presence of four susceptibility residues (two DQA1 Arg 52+ and two DQB1 Asp 57-) conferred the highest relative risk at 20.2. On the other hand, homozygous genotypes for DQA1 non-Arg 52 and DQB1 Asp 57 were found only in the control group. CONCLUSIONS: IDDM susceptibility and resistance in the Egyptian population is strongly associated with the expressed DQ alpha- and beta-heterodimers in a dose-effective manner, as already defined in many different ethnic groups.