Houlston R S, Tomlinson I P, Ford D, Seal S, Marossy A M, Ferguson A, Holmes G K, Hosie K B, Howdle P D, Jewell D P, Godkin A, Kerr G D, Kumar P, Logan R F, Love A H, Johnston S, Marsh M N, Mitton S, O'Donoghue D, Roberts A, Walker-Smith J A, Stratton M F
Institute of Cancer Research, Sutton, Surrey, UK.
Hum Mol Genet. 1997 Aug;6(8):1335-9. doi: 10.1093/hmg/6.8.1335.
A strong HLA association is seen in coeliac disease [specifically to the DQ(alpha10501,beta10201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. One or more genes at HLA-unlinked loci also predispose to coeliac disease and are probably stronger determinants of disease susceptibility than HLA. A recent study has proposed a number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked susceptibility gene. We have examined these regions in 28 coeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus telomeric to HLA. No significant evidence in favour of linkage to coeliac disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing close to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chromosome 15q26 is not strong, the well established association between coeliac disease and insulin dependent diabetes mellitus, together with the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring susceptibility to coeliac disease in some families.
在乳糜泻中可观察到与HLA的强关联（具体为DQ(α10501,β10201异二聚体），但这并不能完全解释患病个体亲属中增加的风险。HLA非连锁位点的一个或多个基因也易患乳糜泻，并且可能是比HLA更强的疾病易感性决定因素。最近一项研究提出了6号染色体p23（与HLA不同）、6号染色体p12、3号染色体q27、5号染色体q33.3、7号染色体q31.3、11号染色体p11、15号染色体q26、19号染色体p13.3、19号染色体q13.1、19号染色体q13.4和22号染色体着丝粒上的一些候选区域，用于定位非HLA连锁的易感基因。我们通过连锁分析在28个乳糜泻家族中研究了这些区域。6号染色体p标记存在过度共享，但没有证据支持HLA端粒存在易感位点。对于3号染色体q27、5号染色体q33.3、7号染色体q31.3、11号染色体p11、19号染色体p13.3、19号染色体q13.1、19号染色体q13.4或22号染色体着丝粒，没有获得支持与乳糜泻连锁的显著证据。然而，在靠近D15S642处存在过度共享。最大非参数连锁分数为1.99（P = 0.03）。尽管乳糜泻与15号染色体q26连锁的证据并不充分，但乳糜泻与胰岛素依赖型糖尿病之间已确立的关联，以及胰岛素依赖型糖尿病易感位点（IDDM3）定位于15号染色体q26，为该区域作为某些家族中赋予乳糜泻易感性的候选位点提供了间接支持。
