Genes for insulin-dependent diabetes mellitus (IDDM) in the major histocompatibility complex (MHC) of African-Americans.
Genes for insulin-dependent diabetes mellitus (IDDM) in the major histocompatibility complex (MHC) of African-Americans.
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非裔美国人主要组织相容性复合体 (MHC) 中胰岛素依赖型糖尿病 (IDDM) 的基因。
DOI：
10.1111/j.1399-0039.1993.tb01980.x
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Stastny,P
中科院分区：
文献类型：
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作者：
Fernandez-Viña,M;Ramirez,LC;Raskin,P;Stastny,P
由于HLA-DR-DQ区域内的强烈连锁不平衡，绘制胰岛素依赖型糖尿病（IDDM）的MHC相关易感性和抵抗因素一直很困难。以前的分析表明，在不同种族中对IDDM相关单倍型的研究可能有助于识别相关基因。我们进行了完整的HLA II类基因分型，以研究34例随机选择的非裔美国人IDDM患者和69例种族匹配的对照者对IDDM的易感性和耐药性。IDDM患者DRB 1 *0301、DRB 1 *0401、DRB 1 * 0405、DQA 1 *0301、DQA 1 * 0302、DQB 1 *0201和DQB 1 *0302均显著升高。DQA 1-DQB 1相关性分析显示，DQA 1 *03与DQB 1 *0201和DQB 1 *0302组合的优势比最高，表明由于顺式和反式编码的异二聚体的形成而产生协同效应。在DR 4亚群中，糖尿病患者中仅DRB 1 *0401和DRB 1 *0405增加。有趣的是，DQB 1 *0602和DQB 1 *0301，以前被认为是编码耐药因子的高加索人，没有显着减少，并删除已知的易感性单倍型后，发现在患者和对照组中具有基本相同的频率。
Mapping the MHC‐associated susceptibility and resistance factors for insulin‐dependent diabetes mellitus (IDDM) has been difficult due to the strong linkage disequilibrium within the HLA‐DR‐DQ region. Previous analyses have suggested that the study of IDDM‐associated haplotypes in different races might be useful for identifying the responsible genes. We have performed complete HLA class II genotyping to study susceptibility and resistance to IDDM in 34 randomly selected African‐American IDDM patients and 69 ethnically‐matched controls. IDDM patients showed highly significant increases of DRB1*0301, DRB1*0401, DRB1*0405, DQA1*0301, DQA1*0302, DQB1*0201 and DQB1*0302. Analysis of DQA1‐DQB1 associations showed that DQA1*03 combined with both DQB1*0201 and DQB1*0302 gave the highest odds ratio, suggesting a synergistic effect due to formation of heterodimers encoded both in cis and in trans. Among the subsets of DR4, only DRB1*0401 and DRB1*0405 were increased in diabetic patients. Interestingly, DQB1*0602 and DQB1*0301, which have previously been thought to encode resistance factors in Caucasians, were not significantly decreased and, after removal of known susceptibility haplotypes, were found to have essentially identical frequencies in patients and controls.