Linkage analysis of candidate regions for coeliac disease genes

A strong HLA association is seen in coeliac disease [specifically to theDQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely accountfor the increased risk seen in relatives of affected cases. One or moregenes at HLA-unlinked loci also predispose to coeliac disease and areprobably stronger determinants of disease susceptibility than HLA. A recentstudy 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 linkedsusceptibility gene. We have examined these regions in 28 coeliac diseasefamilies by linkage analysis. There was excess sharing of chromosome 6pmarkers, but no support for a predisposition locus telomeric to HLA. Nosignificant evidence in favour of linkage to coeliac disease was obtainedfor chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or22cen. There was, however, excess sharing close to D15S642. The maximumnon-parametric linkage score was 1.99 (P = 0.03). Although the evidence forlinkage of coeliac disease to chromosome 15q26 is not strong, the wellestablished association between coeliac disease and insulin dependentdiabetes mellitus, together with the mapping of an IDDM susceptibilitylocus (IDDM3) to chromosome 15q26, provide indirect support for this as acandidate locus conferring susceptibility to coeliac disease in somefamilies.