Polymorphism of the fourth component of complement in Graves' disease and type I diabetes mellitus.

The distribution of major histocompatibility complex (MHC) phenotypes in unrelated patients with Graves' disease or Type I diabetes mellitus and healthy controls was examined. HLA-B8 was increased in both the Graves' disease patients (p = .0018) and diabetes mellitus patients (p = .0246) relative to controls. Although C4AQO is known to show strong linkage disequilibrium with HLA-B8, we could not demonstrate a difference in the frequency of this allele between either group of patients and the controls because the null C4AQO cannot be accurately estimated from phenotype data. An unusual variant C4B3 occurred three times in 117 controls, 10 times in 61 Graves' disease patients (p = .0012) and 13 times in 48 diabetic patients (p = 0.74 X 10(-5]. Although C4B3 is known to show strong linkage disequilibrium with HLA-B15, the frequencies of B15 in the two patient groups did not differ from that of the controls considered here. When 28 MHC haplotypes (supratypes) from 14 unrelated patients with Type I diabetes were compared with 27 non-diabetes supratypes occurring in the same families but not in the patients, 8/28 Type I diabetes supratypes were C4AQOB1+, HLA-B8+, and 4/28 were C4B3+, whereas 1/27 non-diabetes supratypes was C4AQOB1+, B8+, and 0/27 was C4B3+. Of the four C4B3+ diabetes positive supratypes, two were HLA-B15, one was B5 and one was B40. Finally, the second haplotype of 11 diabetes mellitus patients known to carry one high risk C4 haplotype was investigated. The second haplotype was the common type C4A3B1 in only 3/11, whereas at least 5/11 had second haplotypes containing C4BQO, C4B3, C4B2 or C4A*4.(ABSTRACT TRUNCATED AT 250 WORDS)