Immunogenetics of Diabetes Mellitus in Chinese

Abstract

Diabetes Mellitus is a syndrome of hyperglycemia with heterogeneous etiology. Previous reports from population, migration and twin studies suggested that both genetic and environmental factors are all important in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). Among the genetic factors, HLA is the most important and extensively studied. As far as the non-insulin-dependent diabetes mellitus (NIDDM), the etiology remains obscure, though polygenetic factors had been mentioned. Our studies were mainly focused on the assessment of BLA association with diabetes mellitus in Chinese. Preliminary results were shown below: (A)Phenotype association of HLA with IDDM, NIDDM & Maturity-onset diabetes of the young (MODY). There was no significant association of HLA-AB,C alleles with IDDM. DR3 is better associated with IDDM than is DR4 (RR=10.25 vs 3.56) which is the reverse in Caucasian. DR6 is negatively associated with IDDM. No significant association of HLA with NIDDM & MODY. (B)DR heterozygotes association with DM and non-diabetic diseases. Both DR3/4 and 3/9 are significantly associated with juvenile-onset IDDM (RR=47.1 &15.9) and adult-onset IDDM (RR=27.5 &202). The association of DR3/4 is stronger than that DR/9 in both groups. There is no significant association of DR3/4 with NIDDM, MODY and other non-diabetic diseases. (C)Association of BlA-DQαRFLP’S with IDDM. Genomic DNA from patients and controls were digested with EcoRI, Pstl, BamHI and Hindlll and then hybridized with DQα cDNA probe. The results showed 1)significantly increased frequency of EcoRI 13.0 kb, PstIl 9.0 & 4.1 kb and HindIII 4.6 kb in patients 2)significantly decreased frequency of EcoRI 17.0 kb, PstI 17.0 & 10.0 kb, and Hindlll 9.0kb in patients 3)no significant difference in BamHI fragments between IDDM patients and controls. (D)HLA haplotype association with IDDM. IDDM patients are highly associated with DR3 haplotype but not with DR4 haplotype. AW33Bl7CW3DR3DQW2DRW52 may be a high risk haplotype for IDDM in Chinese. (E)Association of non-aspartic acid at position 57 of the HLA-DQβ chain with IDDM and NIDDM. The presence of an amino acid other than aspartic acid at position 57 of the HLA-DQB chain (NA) is highly associated with susceptibility to IDDM in Caucasion but not in Japanese. In Chinese, we demonstrated that HLA-DQB non-ASP-57 allele is significantly associated with IDDM, but not with NIDDM.