Genetic polymorphism of the fourth component of complement and type 1 (insulin-dependent) diabetes.
The complement proteins, Bf, C2, C4A and C4B, are closely linked to HLA. In 74 propositi and their families, and 97 controls genotyped for HLA-A, -B, -C, DR, -Bf, a high incidence of the C4BQ0 variant was detected in the patient group (33% versus 12%, p less than 0.00001); C4BQ0 was more frequent in propositi than in non-affected siblings (40 out of 74 versus 36 out of 92, p less than 0.05). When comparing the distribution of the phenotype C4BQ0 in Type 1 diabetic patients and normal control subjects, the difference was significant in patients bearing DR3 or DR4 (56% and 25%, respectively, p less than 0.003). The main linkage disequilibria were observed among the 74 propositi: B18, BfF1, C4, A3, BQ0, DR3; B12, BfS, C4, A3, BQ0, DR4. The existence of a silent allele at the C4 B locus is known to be associated with a defective immune response.
D003181:Complement C4 / Q000235:genetics*; D015935:Complement C4b; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005787:Gene Frequency; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic
D003181:Complement C4; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II; D015935:Complement C4b