Serjeantson S W, Easteal S
Baillieres Clin Endocrinol Metab. 1991 Jun;5(2):299-320. doi: 10.1016/s0950-351x(05)80129-6.
HLA class II associations with IDDM in populations of non-Caucasoid origin can provide important insights into the nature of the HLA and disease association. Firstly, HLA class II alleles that are rare in Caucasoids but common in other populations can be assessed for their contributory role in IDDM. Secondly, the different HLA class II gene linkage arrangements in different populations can help map the IDDM susceptibility determinants. This chapter reviews studies of HLA class II associations with IDDM in Asian Indians, Chinese, Japanese, Africans and black Americans. Most of these studies have been based on HLA-DR serology. However, DNA analyses, based on restriction fragment length polymorphism, sequence specific oligonucleotide hybridizations of polymerase chain reaction products and DNA sequencing, have made clear the identity of genes contributing to susceptibility or resistance to IDDM in populations of non-Caucasoid origin. DNA sequence analysis of the variable regions of the HLA-DQA, DQB and DRB genes has revealed at least eight alleles at HLA-DQA, 13 at HLA-DQB and 34 at HLA-DRB1. This chapter correlates HLA-DR and DQ allelic diversity with inherited predisposition to IDDM on a global basis. IDDM is strongly associated with the serological specificities of HLA-DQ, rather than with particular amino acid substitutions in class II alleles. DQw8 has a high risk for IDDM, DQw4, DQw5 and DQw9 have a lesser risk, while DQw6 and DQw7 are protective in IDDM. DQw2 is permissive for IDDM, depending on the presence of other HLA class II alleles. Increased heterozygosity at HLA is observed in Oriental patients, as it is in Caucasoid IDDM patients. The nature of this synergism is examined in terms of possible interactive effects between DQA and DQB alleles or DRB and DQB alleles; both effects could be operating. The conclusion from this genetic analysis is that molecular mimicry at HLA-DQ, with either foreign or autoantigens, may be an important mechanism in IDDM. Additionally, the anomalous role of DQw2 in IDDM suggests that a further mechanism, such as T cell activation, may control the ability to mount an immune response against autoantigens. Further studies, possibly with transfectant cell lines, are necessary to clarify the functional role of HLA class II genes in IDDM.
在非白种人起源的人群中，HLA - II类分子与胰岛素依赖型糖尿病（IDDM）的关联能够为HLA与疾病关联的本质提供重要见解。首先，可以评估在白种人中罕见但在其他人群中常见的HLA - II类等位基因在IDDM中的作用。其次，不同人群中不同的HLA - II类基因连锁排列有助于确定IDDM易感性决定因素的位置。本章回顾了亚洲印度人、中国人、日本人、非洲人和美国黑人中HLA - II类分子与IDDM关联的研究。这些研究大多基于HLA - DR血清学。然而，基于限制性片段长度多态性、聚合酶链反应产物的序列特异性寡核苷酸杂交以及DNA测序的DNA分析，已经明确了非白种人起源人群中导致IDDM易感性或抗性的基因。对HLA - DQA、DQB和DRB基因可变区的DNA序列分析显示，HLA - DQA至少有8个等位基因，HLA - DQB有13个，HLA - DRB1有34个。本章在全球范围内将HLA - DR和DQ等位基因多样性与IDDM的遗传易感性相关联。IDDM与HLA - DQ的血清学特异性密切相关，而非与II类等位基因中的特定氨基酸取代相关。DQw8患IDDM的风险高，DQw4、DQw5和DQw9风险较低，而DQw6和DQw7对IDDM有保护作用。DQw2对IDDM是允许的，这取决于其他HLA - II类等位基因的存在。在东方患者中观察到HLA杂合性增加，白种人IDDM患者也是如此。从DQA和DQB等位基因之间或DRB和DQB等位基因之间可能的相互作用效应方面研究了这种协同作用的本质；两种效应可能都在起作用。这种遗传分析的结论是，HLA - DQ处与外来或自身抗原的分子模拟可能是IDDM中的一个重要机制。此外，DQw2在IDDM中的异常作用表明，可能存在另一种机制，如T细胞激活，来控制针对自身抗原产生免疫反应的能力。可能需要进一步用转染细胞系进行研究，以阐明HLA - II类基因在IDDM中的功能作用。
