Multigenic and Overlapping Susceptibilities between IDDM and Cystic Fibrosis Complicated with Diabetes (CF/DM) 397

The incidence of CF/DM (8-12%) is much higher than Type I insulin-dependent diabetes mellitus (IDDM) in the general population. In our preliminary study[J Clin Immunol 14(6):353-358, 1994], the incidence of both DQα and DQβ genotypes in the CF/DM population (n=26) were in disequilibrium when compared with normal controls (n=517) and the CF/non-DM population (n=42). In a patientmatched, total ascertainment study, an increased frequency of the Asp^57- allele, DQB1 *0201 was determined (40.4% versus 28.0% for CF/DM and CF/non-DM). The IDDM protective Asp⁵⁷⁺ alleles were lower in the CF/DM versus CF/non-DM (p≤ 0.025) or normal controls (p≤0.008). The interpretation of these results suggests a potential conflict. Why does an autoimmune disease (IDDM) show similar involvement of specific alleles of the major histocompatibility class II (MHC II) loci as CF/DM, a non-autoimmune diabetes? This conflict is being addressed by assessing other known diabetogenic risk genes within the MHC II and comparing the results between normals, IDDM and CF/DM. Additionally, a continuing multi center study (10 National CF Clinical Centers) of CF/DM using a matched-design (n=139 CF/DM and n=300 CF/non-DM), is planned to confirm the original result and to identity other candidate diabetogenic susceptibility genes. This project was supported in part by a grant from Allegheny-Singer Research Institute.