INHERITANCE OF MHC CLASS-II GENES IN IDDM STUDIED IN POPULATION-BASED AFFECTED AND CONTROL FAMILIES

The transmission of HLA-DR and DQ was compared between 46 families with at least one child affected by insulin dependent diabetes mellitis (IDDM) and 43 healthy control families. In the patient families, there was an increased transmission of DR4 (p < 0.025) and DQB1*0302 (p < 0.01) from both parents to the index patient. There was an increased transmission of DQB1*0302 (p < 0.03) from the mothers only. The non-inherited maternal haplotypes showed a significantly decreased frequency (p < 0.01) of positively associated haplotypes (DR4-DQA1* 0301-DQB1*0302, DR3-DQA1*0501-DQB1*0201) compared to all parental haplotypes in the control families. In the control families neither transmission rates nor frequencies of non-inherited haplotypes differed from those expected in the control families. In conclusion, the observed reduction of IDDM-positively associated haplotypes in patient non-inherited maternal haplotypes, but not in non-inherited paternal haplotypes, suggests that tolerance during fetal life to maternal non-inherited HLA molecules may be important to diabetes development.