An Explanation for the Neutral Effect of DR2 on IDDM Susceptibility in Central Italy
An Explanation for the Neutral Effect of DR2 on IDDM Susceptibility in Central Italy
复制标题
DR2 对意大利中部 IDDM 易感性中性影响的解释
作者：
R. Sorrentino;U. de Grazia;R. Buzzetti;L. Nisticò;C. Iannicola;S. Costanzi;R. Tosi
IDDM的易感性与HLA密切相关。一些HLA等位基因组合（单倍型）可以在大多数患者中发现，而其他单倍型很少遇到。已经提出，这种易感性的差异取决于DQ β链中Asp 57的缺失（在DR 3和DR 4单倍型中）或存在（在DR 2单倍型中）。南欧人群的数据挑战了这一假设，因为DR 2单倍型与IDDM没有负相关，如北方欧洲人群所报道的那样。本研究选择了一组DR 2阳性的意大利IDDM患者，结果显示21个DR 2单倍型中有19个（90.5%）具有非Asp 57 DQB等位基因。此外，相同的非Asp 57亚型在DR 2阳性的健康意大利人群中也具有相对较高的频率（9/28，或32.1%，DR 2单倍型）。患者与对照组比较差异有显著性意义（x < 0.0001）。这是迄今为止分析的最大的DR 2阳性患者系列。在各种白色人群的累积数据比较显示了一个明显的北方欧洲南部的梯度。在欧洲南部，非Asp 57 DR 2亚型的相对频率增加。同时，DR 2单倍型的明显保护作用消失。因此，观察到的白色人群中DR 2-IDDM相关性的差异可以通过Asp 57假说充分解释，本研究的数据强烈支持Asp 57假说。
Susceptibility to IDDM is strongly associated with HLA. Some HLA allelic combinations (haplotypes) can be found in most patients, whereas other haplotypes are encountered only rarely. It has been proposed that this difference in susceptibility depends on the absence (in the DR3 and DR4 haplotypes) or the presence (in the DR2 haplotype) of Asp57 in the DQ β-chain. Data on southern European populations challenge this hypothesis because the DR2 haplotype has not been associated negatively with IDDM, as reported in northern European populations. This study on a selected panel of DR2-positive Italian IDDM patients shows that 19 of 21 (90.5%) DR2 haplotypes possess a non-Asp57 DQB allele. Moreover, the same non-Asp57 subtype has a comparatively high frequency (9/28, or 32.1%, DR2 haplotypes) also in the DR2-positive healthy Italian population. The difference between patients and control subjects is significant (xP < 0.0001). This is the largest series of DR2-positive patients analyzed so far. Comparison with cumulated data in various white populations shows a distinct northern European-to-southern European gradient. Toward southern Europe, the relative frequency of the non-Asp57 DR2 subtype increases. Concomitantly, the apparent protective effect of the DR2 haplotype disappears. Therefore, the observed differences in DR2-IDDM association in white populations can be explained adequately by the Asp57 hypothesis, which this study's data strongly support.
胰岛素依赖型糖尿病中的 DR2 单倍型：DNA 限制性片段长度多态性分析。
影响因子：
2.7
作者：
Segall,M;Noreen,H;Schluender,L;Swenson,M;Barbosa,J;Bach,FH
通讯作者：
Bach,FH
胰岛素依赖性糖尿病相关 HLA-D 区域编码的决定簇。
影响因子：
2.7
作者：
Bach,FH;Rich,SS;Barbosa,J;Segall,M
通讯作者：
Segall,M
一种新的 HLA-DR2 扩展单倍型与胰岛素依赖性糖尿病易感性有关。
影响因子：
2.7
作者：
Carcassi,C;Trucco,G;Trucco,M;Contu,L
通讯作者：
Contu,L