HLA TYPING AND RESULTS OF LINKAGE ANALYSIS TO CHROMOSOME 6p IN 72 KINDRED WITH CELIAC DISEASE

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4 Celiac disease is known to be familial and has a strong genetic association with the HLA antigens DR3 and DQ2 (DQA1*501 DQB1*0201). However, it has been proposed that the HLA association alone is insufficient to explain the hereditary nature of celiac disease. The aims of our study were to: 1) determine the proportion of familial aggregation of celiac disease accounted for by the known HLA association, 2) attempt to confirm the previously reported non-HLA linkage to chromosome 6p. We evaluated 195 CD patients from 72 kindred by DNA based HLA typing for DQA and DQB. Patients were classified into 2 groups: 1) stringent criteria - patients with positive biopsy and/or positive endomysial antibody; 2) broad criteria - the patients in the stringent criteria group plus cases diagnosed by response to diet alone. A series of 10 markers encompassing the HLA region on chromosome 6p were genotyped and linkage analysis was performed. Patients with stringent criteria for diagnosis demonstrated a high risk HLA type in 93.1% of cases compared to 81% in cases diagnosed using broad criteria. This indicates a high likelihood of misdiagnosis in cases diagnosed by response to diet alone. DQB1*0201 was found significantly more frequently than DQA1*0501 in the stringent criteria group, indicating additional risk conferred by DQB1*0201. Strong evidence for linkage at the HLA region of chromosome 6 was seen in both groups. We were unable to confirm previous reports of linkage to 6p23 (a non-HLA region).