COMBINATIONS OF SPECIFIC DRB1, DQA1, DQB1 HAPLOTYPES ARE ASSOCIATED WITH INSULIN-DEPENDENT DIABETES-MELLITUS IN SARDINIA
COMBINATIONS OF SPECIFIC DRB1, DQA1, DQB1 HAPLOTYPES ARE ASSOCIATED WITH INSULIN-DEPENDENT DIABETES-MELLITUS IN SARDINIA
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DOI：
10.1016/0198-8859(93)90146-r
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发表时间：
1993-06-01
期刊：
影响因子：
2.7
通讯作者：
CONGIA, M
中科院分区：
文献类型：
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作者：
CUCCA, F;MUNTONI, F;CONGIA, M
撒丁岛人口的胰岛素依赖型糖尿病发病率极高（0- 14岁年龄组每10万人中有30.2人）。本研究报告了120例散发性胰岛素依赖型糖尿病患者和89例撒丁岛健康受试者的HLA II类基因的分子特征。与其他白种人相比，撒丁岛患者和对照组的单倍型和基因型分布异常。特别是，在患者（0.58）和对照（0.23）中，DRB 1 *0301、DQA 1 *0501、DQB 1 *0201易感性单倍型的基因频率都很高，而在健康人群中观察到DRB 1 *1501、DQA 1 *0102、DQB 1 *0602保护性单倍型的减少（0.03）。这种分布可能部分解释了撒丁岛报告的IDDM的高发病率。DQ β 57和DQ α 52残基的分析表明，Asp 57的缺失和Arg 52的存在以剂量-反应方式与IDDM相关。另一方面，我们发现：（a）当将撒丁岛人与另一个来自相同纬度但IDDM发病率较低的健康高加索人群体进行比较时，发现这些残基的分布非常相似;（B）编码相同DQ α 52/DQ β 57表型的几种基因型携带非常不同的相对风险; DRB 1 *0403、DQA 1 *0301、DQB 1 *0304单倍型（DQ β 57 Asp-neg和DQ α 52 Arg-pos）在40%的DR 4阳性对照中发现，但在患者中未发现。（p = 0.00034），而在70%的DR 4阳性患者和仅一个对照中发现在相同位置携带相同残基的DRB 1 *0405、DQA 1 *0301和DQB 1 *0302单倍型（p = 0.00003）。这些结果表明，胰岛素依赖型糖尿病的易感性不能完全解释的模型，其中只有DQ α 52和DQ β 57残基被考虑在内。
The Sardinian population has an extremely high incidence of IDDM (30.2 of 100.000 in the age group of 0- 14 years). This study reports the molecular characterization of HLA class II genes in 120 IDDM sporadic patients and 89 healthy subjects of Sardinian origin. Compared with other Caucasians, both Sardinian patients and controls had an unusual distribution of haplotypes and genotypes. In particular, there was a high gene frequency of the DRB1*0301, DQA1*0501, DQB1*0201 susceptibility haplotype both in patients (0.58) and controls (0.23) while a reduction of the DRB1*1501, DQA1*0102, DQB1*0602 protective haplotype (0.03) was observed in the healthy population. This distribution may partially explain the high incidence of IDDM reported in Sardinia. The analysis of the DQbeta57 and DQalpha52 residues showed that the absence of Asp 57 and the presence of Arg 52 were associated with IDDM in a dose-response manner. On the other hand, we found that (a) a very similar distribution of these residues was found when comparing Sardinians with another healthy Caucasian population from the same latitude but with a lower rate of IDDM incidence; (b) several genotypes encoding the identical DQalpha52/DQbeta57 phenotype carried very different relative risks; and (c) the DRB1*0403, DQA1*0301, DQB1*0304 haplotype (DQbeta57 Asp-neg and DQalpha52 Arg-pos) was found in 40% of the DR4-positive controls but not in patients (p = 0.00034), while the DRB1*0405, DQA1*0301, and DQB1*0302 haplotype carrying the same residues at the same positions was found in 70% of the DR4-positive patients and in only one control (p = 0.00003). These findings suggest that IDDM susceptibility cannot be completely explained by the model in which only DQalpha52 and DQbeta57 residues are taken into account.