Cystic fibrosis-related diabetes is associated with HLA DQB1 alleles encoding Asp-57- molecules.
The incidence of insulin-dependent diabetes in individuals with cystic fibrosis is nearly 100 times greater than in the general population. In the latter group, strong associations with specific HLA DQA1 and DQB1 alleles have been observed. To determine if a similar distribution of alleles occurs in cystic fibrosis patients with diabetes, a cohort of these individuals was typed for DQA1 and DQB1 alleles. HLA DQB1*0201 (Asp57-) was more frequent in diabetics compared to controls (40.4 vs 28%), while the frequency of alleles encoding Asp57+ molecules was lower in diabetics relative to both the cystic fibrosis-only controls (P = 0.025) and the general population (P = 0.008). The presence of at least one protective DQA1-DQB1 heterodimer (i.e., Arg52- and Asp57+, respectively) in cis or trans was significantly lower in the diabetics than in either of the control groups. Thus, the HLA alleles known to be associated with insulin-dependent diabetes mellitus in the general population are also found in diabetics with cystic fibrosis.
Carrington
M
M
Biological Carcinogenesis and Development Program, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.
Krueger
L J
LJ
Holsclaw
D S
DS
Iannuzzi
M C
MC
Dean
M
M
Mann
D
D
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics*; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen