LINKAGE ANALYSIS OF CANDIDATE REGIONS FOR CELIAC-DISEASE GENES

A strong HLA association is seen in coeliac disease [specifically to t he DQ(alpha 10501,beta 1*0201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. On e or more genes at HLA-unlinked loci also predispose to coeliac diseas e and are probably stronger determinants of disease susceptibility tha n HLA. A recent study has proposed a number of candidate regions on ch romosomes 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 c oeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus te lomeric to HLA. No significant evidence in favour of linkage to coelia c disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19 p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing c lose to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chrom osome 15q26 is not strong, the well established association between co eliac disease and insulin dependent diabetes mellitus, together with t he mapping of an IDDM susceptibilty locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring sus ceptibilty to coeliac disease in some families.