Complex association analysis of Graves disease using a set of polymorphic markers

Graves disease is complex autoimmune thyrotoxicosis. A number of genes may contribute to the development of the disorder. Some of them may be genes th at encode cytotoxic T-lymphocyte-associated serine esterase-4 (CTLA4), subu nit 2 of large multifunctional protease (LMP2), thyroid-stimulating hormone receptor (TSHR), and interleukin 1 receptor antagonist (IL1RN). We studied polymorphism of Ala17Thr CTLA4, H60R LMP2, Pro52Thr TSHR, and IL1RN-VNTR i n healthy controls (n = 93) and patients with Graves disease (n = 78) using PCR. To study CTLA4, H60R, and TSHR polymorphism, PCR products were digest ed with MboI, Hin6I and PsyI, respectively. Comparative analysis using chi( 2) test showed significant differences in allele and genotype frequency of Ala17Thr polymorphic marker between the two groups studied. Thus, the CTLA4 gene may be involved in the pathogenesis of Graves disease in a Moscow pop ulation. (C) 2000 Academic Press.