Mannion A, Stevens F M, McCarthy C F, Grimes-O'Cearbhaill H, Killeen A A
Department of Immunology, University College Hospital, Galway, Ireland.
Am J Med Genet. 1993 Feb 1;45(3):373-7. doi: 10.1002/ajmg.1320450319.
The highest reported prevalence of celiac disease (gluten-sensitive enteropathy) is found in the West of Ireland. Recent genetic data have suggested that major histocompatibility complex-linked loci may have a dominant genetic effect for disease susceptibility in this population compared with a recessive effect in other groups. To further understand the role of the MHC in celiac disease in the West of Ireland, we analyzed markers for 22 MHC haplotypes from celiac patients and compared them with 18 nontransmitted haplotypes found in the parents of celiac children, and with reported haplotypes from other populations. An extended MHC haplotype including [HLA-B8, DR3, DQw2, BfS, C4AQ0, and C4B*1] accounted for 50% of celiac haplotypes but only 27% of nontransmitted parental haplotypes. Compared with other reported haplotypes in celiacs, patients from the West of Ireland show a higher prevalence of HLA-A1 as a component of this extended haplotype, suggesting that although the core haplotype is similar between Irish patients and others, the celiac population in the West of Ireland differs at other HLA loci. We did not observe any other common haplotypes among our patients unlike the situation in other populations. These differences may underlie the possible dominant effect of HLA-linked loci and the unusually high prevalence of celiac disease in the Irish population. We also found that the serum levels of complement components C3c, C4, and factor B were significantly lower among celiac patients than nonceliacs. The lower serum level of C4 appears to be related to the presence of deletions and null alleles at the C4A and C4B loci in celiacs.
据报告，乳糜泻（麸质敏感肠病）发病率最高的地区是爱尔兰西部。最近的基因数据表明，与其他群体中的隐性效应相比，主要组织相容性复合体连锁基因座可能对该人群的疾病易感性具有显性遗传效应。为了进一步了解主要组织相容性复合体（MHC）在爱尔兰西部乳糜泻中的作用，我们分析了乳糜泻患者22种MHC单倍型的标记，并将其与乳糜泻儿童父母中发现的18种未传递单倍型以及其他人群报告的单倍型进行比较。一种扩展的MHC单倍型，包括[HLA - B8、DR3、DQw2、BfS、C4AQ0和C4B*1]，占乳糜泻单倍型的50%，但在未传递的亲代单倍型中仅占27%。与乳糜泻患者中其他报告的单倍型相比，爱尔兰西部的患者作为这种扩展单倍型的一个组成部分，HLA - A1的患病率更高，这表明尽管爱尔兰患者与其他患者的核心单倍型相似，但爱尔兰西部的乳糜泻人群在其他HLA基因座上存在差异。与其他人群的情况不同，我们在患者中未观察到任何其他常见单倍型。这些差异可能是HLA连锁基因座可能的显性效应以及爱尔兰人群中乳糜泻异常高发病率的基础。我们还发现，乳糜泻患者血清中的补体成分C3c、C4和B因子水平显著低于非乳糜泻患者。C4血清水平较低似乎与乳糜泻患者C4A和C4B基因座上的缺失和无效等位基因的存在有关。
