The genetic structure of the C4 region is itself complex and highly polymorphic with both allelic and copy number variation of C4A and C4B genes.46 Genetic variation in C4 is known to contribute to disease susceptibility associated with MHC haplotypes47–49, but other MHC genes are also likely to be involved.34, 48 In addition to systemic diseases such as pSS and SLE, the MHC 8.1 haplotype is associated with a number of organ-specific autoimmune diseases such as type 1 diabetes mellitus, Hashimoto’s thyroiditis, Graves’ disease, myasthenia gravis and multiple sclerosis. This evidence concerns the gene HLA-C and Graves disease.