Complement C4 and heat shock protein 70 (HSP70) genotypes and type I diabetes mellitus.

Type I diabetes is strongly associated with the major histocompatibility complex (MHC) class II region (DR and DQ loci), and to a lesser extent the class III region (complement C4 loci). Restriction fragment length polymorphism analysis was employed to investigate the C4 and heat shock protein 70 (HSP70) loci of 176 patients with type I diabetes and 92 healthy controls. In the patient population there was an excess of deletions of the C4A locus (48.5% vs 22.1%, P less than 0.0005). The HSP70 probe in conjunction with the restriction endonuclease Pst I detects two alleles of 9 or 8.5 kilobases (kb). The 8.5 kb allele was significantly increased in the patient group compared to healthy controls (0.569 vs 0.353, respectively, P less than 0.0005). Furthermore, a C4A deletion nearly always occurred with the 8.5 kb HSP70 allele, suggesting that it may be a marker of the HLA-A1,B8,C4A deletion, DR3 extended haplotype.