HLA-DQA_1、-DQB_1等位基因在IDDM易感性中的作用

HLA-DQA AND DQB ALLELES CONTRIBUTE TO SUSCEPTIBILITY TO IDDM

运用序列特异性寡核苷酸探针23个,其中DQA_19个,DQB_114个,对48例IDDM及46例正常对照的白细胞DNA PCR扩增产物进行斑点杂交,检验DQA_1及DQB_1等位基因。发现HLA-DQ_α_(52^-)精氨酸及DQβ_(57^-)非天门冬氨酸的频率在IDDM中显著增高,与IDDM易感性高度相关。DQβ_(57^-)天门冬氨酸在IDDM中显著减少,似对IDDM的发病有“抵抗”作用。与白种人相比,NA/NA纯合子在IDDM中的频率显著低于白种人。A/A纯合子的频率又显著高于白种人。因此,DQ一个氨基酸的改变只是华人IDDM易感性的一个重要相关因素,不是唯一主要因素。

Insulin-dependent diabetes mellitus (IDDM) is strongly associated with the presence of arginine in position 52 of the DQα chain and with the absence of the aspartic acid in position 57 of the DQβ chain in the white people. With the aim of confirming this association in Chinese.the extensive oligonucleotide dot-blot hybridization of PCR-amplified DQA, and DQB1 genes were studied in 48 IDDM patients and 46 healthy non-diabetic control subjects. Three major findings emerged from our analysis. 1)DQα52-Arg and DQβ57-non-Asp were strongly associated with IDDM susceptibility, and showed statistical significance as compared with controls (P<0. 001 and P<0. 005 respectively). 2)DQβ57-non-Asp homozygous (NA/NA) is associated with increased susceptibility to IDDM (22. 9% vs 2. 2% in controls,P <0. 01).DQβ57-Asp homozygous (A/A) is associated with protection against IDDM (14. 6% vs 47. 8% in controls,P<0. 01). 3)In this study,about 14. 6% of IDDM were homozygous for DQβ57-Asp,compared with 0% in American patients. Only 22. 9% of IDDM were homozygous for β357-non-Asp,compared with 96% of American diabetic subjects in the previous study. Thus,it is unlikely that DQb57 amino acid has a major effect on IDDM susceptibility among the Chinese.