Park Y S, Wang C Y, Ko K W, Yang S W, Park M, Yang M C, She J X
Department of Internal Medicine and Pediatrics, Hanyang University College of Medicine, Seoul, Korea.
Hum Immunol. 1998 Dec;59(12):794-801. doi: 10.1016/s0198-8859(98)00076-7.
The association of HLA-DRB1 and DQB1 genes with IDDM in Koreans was assessed using 115 IDDM patients and 140 nondiabetic controls. DQB10201 is the only DQB1 allele positively associated with IDDM while DQB0602, 0601 and 0301 are negatively associated. Three DRB1 alleles (DRB10301, DRB10407 and DRB10901) are positively associated while four DR allele groups (DRB115, DRB112, DRB110 and DRB114) are negatively associated. However, Haplotype analyses indicated that DQB10302, DRB10405 and DRB10401 may confer susceptibility because the DRB10405-DQB0302 and DRB10401-DQB10302 haplotypes are positively associated with the disease. The lack of association in Koreans with the DQB10302 allele, which appears predisposing in studies of non-Orientals, is due to its strong linkage disequilibrium (LD) with the protective DRB10403 and 0406 alleles, while the lack of association with DRB10405 is because of its strong LD with the protective DQB1*0401 allele. Nine DR/DQ genotypes confer significantly increased risk to IDDM. Seven of the nine genotypes (DR3/4s, DR1/4s, DR4s/13, DR4s/8, DR4s/7, DR9/13 and DR3/9) were also found to be at high risk to IDDM in other populations, while the two others (DR1/9 and DR9/9) are only found in Koreans. Surprisingly, DR4/4 homozygotes are not associated with high risk to IDDM in Koreans. This observation can be explained by the high frequency of protective DR4 subtypes and the protective DQ alleles (0301 and 0401) associated with the susceptible DR4 alleles. Our analyses indicate that the counterbalancing act between susceptible DRB1 and protective DQB1, and vice versa, that has already been observed in Chinese and Japanese, is the major factor responsible for the low incidence of diabetes in Koreans.
利用115例胰岛素依赖型糖尿病（IDDM）患者和140例非糖尿病对照，评估了韩国人群中HLA - DRB1和DQB1基因与IDDM的关联。DQB10201是唯一与IDDM呈正相关的DQB1等位基因，而DQB0602、0601和0301呈负相关。三个DRB1等位基因（DRB10301、DRB10407和DRB10901）呈正相关，而四个DR等位基因组（DRB115、DRB112、DRB110和DRB114）呈负相关。然而，单倍型分析表明，DQB10302、DRB10405和DRB10401可能赋予易感性，因为DRB10405 - DQB0302和DRB10401 - DQB10302单倍型与该疾病呈正相关。在韩国人群中，DQB10302等位基因缺乏关联，而在非东方人群的研究中该等位基因似乎具有易感性，这是由于它与保护性DRB10403和0406等位基因存在强连锁不平衡（LD），而与DRB10405缺乏关联是因为它与保护性DQB1*0401等位基因存在强LD。九种DR/DQ基因型使IDDM风险显著增加。这九种基因型中的七种（DR3/4s、DR1/4s、DR4s/13、DR4s/8、DR4s/7、DR9/13和DR3/9）在其他人群中也被发现对IDDM具有高风险，而另外两种（DR1/9和DR9/9）仅在韩国人群中发现。令人惊讶的是，在韩国人群中DR4/4纯合子与IDDM高风险无关。这一观察结果可以通过保护性DR4亚型以及与易感DR4等位基因相关的保护性DQ等位基因（0301和0401）的高频率来解释。我们的分析表明，在中国人和日本人中已经观察到的易感DRB1和保护性DQB1之间的平衡作用，反之亦然，是韩国人糖尿病发病率低的主要原因。
