Hernández J L, Michalski J P, McCombs C C, McCarthy C F, Stevens F M, Elston R C
Department of Biometry and Genetics, Louisiana State University Medical Center, New Orleans 70112-1393.
Genet Epidemiol. 1991;8(1):13-27. doi: 10.1002/gepi.1370080103.
Although coeliac disease (CD) is strongly associated with the HLA alleles B8 and DR3, the genetic basis of this illness remains obscure. Recent studies show that at least two unlinked loci are involved. Most studies agree on recessivity at the HLA-unlinked locus but differ with respect to dominance or recessivity at the HLA-linked disease susceptibility locus. To address this controversy, we examined the association of CD with HLA in 39 families from the West of Ireland. Previous studies have shown that the prevalence of CD and the frequencies of the HLA antigens associated with it are higher in this population than in most others. Analysis of the data revealed a significant excess of concordant sib-pairs with two HLA haplotypes in common and an excess of discordant pairs with no haplotype in common. Chi-square tests confirmed a highly significant association between HLA-B8 and CD. Both heterozygotes and homozygotes for B8 had a significantly increased risk of CD. The risk for homozygotes was slightly higher than for heterozygotes, although not significantly so. The segregation ratio for disease occurrence among sibs of probands was estimated to be 0.185 when neither parent is affected. We estimated a gene frequency of 0.003 for the disease allele (C) at the HLA-linked locus and of 0.648 for the disease allele (d) at the HLA-unlinked locus. Assuming that CCdd homozygotes are always affected and that only carriers of C who are homozygous dd can be affected, the disease was found to be completely penetrant in Ccdd heterozygotes. These results support dominance at the HLA-linked locus conferring susceptibility to CD. Possible reasons for the discrepancy between the West of Ireland and other populations are discussed.
尽管乳糜泻（CD）与HLA等位基因B8和DR3密切相关，但这种疾病的遗传基础仍不清楚。最近的研究表明，至少有两个不连锁的基因座参与其中。大多数研究都认同HLA不连锁基因座的隐性遗传，但在HLA连锁疾病易感基因座的显性或隐性方面存在分歧。为了解决这一争议，我们对来自爱尔兰西部的39个家庭进行了CD与HLA的关联研究。先前的研究表明，该人群中CD的患病率以及与之相关的HLA抗原频率高于大多数其他人群。数据分析显示，有两个共同HLA单倍型的同卵双生子对显著过多，而没有共同单倍型的异卵双生子对也过多。卡方检验证实HLA - B8与CD之间存在高度显著的关联。B8的杂合子和纯合子患CD的风险均显著增加。纯合子的风险略高于杂合子，尽管差异不显著。当父母均未患病时，先证者同胞中疾病发生的分离比估计为0.185。我们估计HLA连锁基因座上疾病等位基因（C）的基因频率为0.003，HLA不连锁基因座上疾病等位基因（d）的基因频率为0.648。假设CCdd纯合子总是患病，且只有C的携带者且为dd纯合子才会患病，发现疾病在Ccdd杂合子中完全显性。讨论了爱尔兰西部与其他人群之间差异的可能原因。
