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

The transmission of HLA-DR and DQ was compared between 46 families wit h 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 DQB10302 (p < 0. 01) from both parents to the index patient. There was an increased tra nsmission of DQB10302 (p < 0.03) from the mothers only. The non-inher ited maternal haplotypes showed a significantly decreased frequency (p < 0.01) of positively associated haplotypes (DR4-DQA1 0301-DQB1*0302 , DR3-DQA10501-DQB1*0201) compared to all parental haplotypes in the control families. In the control families neither transmission rates n or frequencies of non-inherited haplotypes differed from those expecte d in the control families. In conclusion, the observed reduction of ID DM-positively associated haplotypes in patient non-inherited maternal haplotypes, but not in non-inherited paternal haplotypes, suggests tha t tolerance during fetal life to maternal non-inherited HLA molecules may be important to diabetes development.