HUMAN-LEUKOCYTE ANTIGEN CLASS-II POLYMORPHISMS AND GENETIC SUSCEPTIBILITY OF IDDM IN EGYPTIAN CHILDREN

OBJECTIVE- To analyze the association between human leukocyte antigen (HLA) and insulin-dependent diabetes mellitus (IDDM) in the Egyptian p opulation for the first time and, thus, to determine the frequency of risk-associated alleles identified by a genomic HLA class II typing. E gyptians are genetically classified as North Africans and considered t o be between Caucasoids and Africans (closer to Caucasoids). RESEARCH DESIGN AND METHODS- HLA class II typing was performed for 50 IDDM pati ents 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 seq uence oligonucleotide hybridization. RESULTS- The frequency of DRB103 01-DRB30201-DQA1*0501-DQB1* 0201 haplotype was 43.9% in the IDDM pati ents and 7.1% in the control subjects (P < 0.00001), reflecting the in creased prevalence of DQA10501 susceptibility allele coding for argin ine (Arg) in position 52 and DQB10201 susceptibility allele noncoding aspartic acid (Asp) at position 57. Alleles DQB10601 and 0603, both carrying Asp at, position 57 of the beta-chain, and DQA10103, encodin g a non-Arg 52 alpha-chain, were significantly decreased among the IDD M 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 suscep tibility and resistance in the Egyptian population is strongly associa ted with the expressed DQ alpha- and beta-heterodimers in a dose-effec tive manner, as already defined in many different ethnic groups.