A GENE IN THE HLA CLASS-I REGION CONTRIBUTES TO SUSCEPTIBILITY TO IDDM IN THE FINNISH POPULATION
A GENE IN THE HLA CLASS-I REGION CONTRIBUTES TO SUSCEPTIBILITY TO IDDM IN THE FINNISH POPULATION
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DOI：
10.1007/bf00400951
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发表时间：
1994-09-01
期刊：
影响因子：
8.2
通讯作者：
WETTENSTRAND, G
中科院分区：
文献类型：
--
作者：
FENNESSY, M;METCALFE, K;WETTENSTRAND, G
在芬兰，单倍型A2、Cw 1、B56、DR 4、DQ 8是胰岛素依赖型糖尿病（IDDM）患者中第三常见的单倍型，并且具有最高的单倍型特异性绝对危险度。Cw 1、B56、DR 4、DQ 8单倍型中含有A2以外的HLA-A等位基因在人群中并不常见，与IDDM无关。A2和非A2单倍型在DNA水平上的比较表明，它们在HLA-B、-DR和-DQ位点上是相同的。I类等位基因赋予IDDM易感性的证据来自芬兰最常见于IDDM患者的两种HLA-C、-B、-DR和-DQ单倍型。Cw 3、B62、DR 4、DQ 8单倍型上的A24、A3、A2和Cw 7、B8、DR 3、DQ 2单倍型上的A28、A2、A1均与IDDM相关。在芬兰，这七种单倍型，包括A2、Cw 1、B56、DR 4、DQ 8，占糖尿病单倍型的33%和非糖尿病单倍型的10.3%（p < 0.00001）。I类区域对IDDM易感性的贡献在缺乏疾病易感性II类等位基因的IDDM患者中也很明显。与非DR 3/非DR 4对照受试者（58例中的40例; p = 0.038）相比，非DR 3/非DR 4 IDDM患者（55例中的47例）具有两个IDDM相关HLA-A等位基因。此外，与对照组（20例中的12例; p = 0.056）相比，经寡聚型分析证实不能形成“糖尿病易感性”DQ异源二聚体的IDDM患者倾向于拥有两个糖尿病相关的HLA-A等位基因（13例中的12例）。
In Finland the haplotype A2, Cw1, B56, DR4, DQ8 is the third most common haplotype in insulin-dependent diabetic (IDDM) patients and has the highest haplotype-specific absolute risk for IDDM. Cw1, B56, DR4, DQ8 haplotypes containing HLA-A alleles other than A2 are infrequent in the population and are not associated with IDDM. Comparison of the A2 and non-A2 haplotypes at the DNA level showed that they were identical at HLA-B, -DR, and -DQ loci. Evidence that class I alleles confer susceptibility to IDDM was obtained from the two HLA-C, -B, -DR and -DQ haplotypes most frequently found in IDDM patients in Finland. A24, A3 and A2 on the Cw3, B62, DR4, DQ8 haplotype, and A28, A2 and A1 on the Cw7, B8, DR3, DQ2 were all found to be associated with IDDM. In Finland these seven haplotypes, including A2, Cw1, B56, DR4, DQ8, account for 33 % of diabetic haplotypes and 10.3 % of non-diabetic haplotypes (p < 0.00001). The contribution of the class I region to IDDM susceptibility was also apparent in those IDDM patients lacking the disease-predisposing class II alleles. Significantly more non-DR3/non-DR4 IDDM patients (47 of 55) possessed two of the IDDM-associated HLA-A alleles compared to non-DR3/non-DR4 control subjects (40 of 58; p = 0.038). Moreover, IDDM patients confirmed by oligotyping as unable to form a 'diabetes-susceptibility' DQ heterodimer, tended to possess two diabetes-associated HLA-A alleles (12 of 13) compared to control subjects (12 of 20; p = 0.056).