HLA-DQB1*0201/0302 is associated with severe retinopathy in patients with IDDM
HLA-DQB1*0201/0302 is associated with severe retinopathy in patients with IDDM
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DOI：
10.1007/s001250050575
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发表时间：
1996-11-01
期刊：
影响因子：
8.2
通讯作者：
Lernmark, A
中科院分区：
文献类型：
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作者：
Agardh, D;Gaur, LK;Lernmark, A
一些胰岛素依赖型糖尿病（IDDM）患者会出现严重的视网膜病变。假定的危险因素如高血压、代谢控制不良、肾病和生长激素水平不能完全解释这些患者视网膜病变的进展。由于一些没有任何已知易感危险因素的糖尿病患者会发展为严重的视网膜病变，而另一些患者则不会。在本研究中，我们比较了两组IDDM患者的HLA-DR和DQ，一组为早发性糖尿病患者，患有严重的非增殖性或增殖性视网膜病变；另一组没有或只有轻微的视网膜病变迹象。采用聚合酶链反应（PCR）和等位基因特异性探针杂交进行高分辨率HLA分型。DR3-DQ2单倍型DRB1*0301、DQA1*0501和DQB1*0201在重度视网膜病变患者中更为常见。DQA1*03/0501基因型与DQB1*0201/0302基因型的某些等位基因组合存在差异（p < 0.05），提示DQB1*0201/0302是重度视网膜病变最强的遗传标记，而DRB1*0301/0401仅与该基因型组合时具有次要影响。DR3-DQ2/DR4-DQ8基因型（DRB1*0301-DQA1*0501-DQB1*0201/DRB1*0401-DQA1*03-DQB1*0302）阳性的IDDM患者发生严重视网膜病变的风险更高。
Some insulin-dependent diabetic (IDDM) patients develop severe forms of retinopathy. Putative risk factors such as hypertension, poor metabolic control, nephropathy and growth hormone levels do not fully explain the progress of retinopathy in these patients. It has been discussed whether there is a genetic marker, since some diabetic patients without any known predisposing risk factors develop severe retinopathy and others do not, In the present study, HLA-DR and DQ were compared in two patient groups with IDDM, One group consisted of patients with early-onset diabetes, with severe non-proliferative or proliferative retinopathy; the other group had no or only mild signs of retinopathy. High resolution HLA typing was carried out by polymerase chain reaction (PCR) and hybridization with allele specific probes. Alleles on the DR3-DQ2 haplotype, DRB1*0301, DQA1*0501 and DQB1*0201, were more frequent in patients with severe retinopathy. A difference was seen when combining certain alleles in the genotypes of DQA1*03/0501 (p > 0.05) and DQB1*0201/0302 (p < 0.01), The findings of the present study suggest that DQB1*0201/0302 is the strongest genetic marker for severe retinopathy and DRB1*0301/0401 only has a secondary influence when combined with this genotype. It seems as if IDDM patients who are positive for the genotype DR3-DQ2/DR4-DQ8 (DRB1*0301-DQA1*0501-DQB1*0201/DRB1*0401-DQA1*03-DQB1*0302) are at greater risk of developing severe retinopathy.