A CTLA-4 GENE POLYMORPHISM IS ASSOCIATED WITH BOTH GRAVES-DISEASE ANDAUTOIMMUNE HYPOTHYROIDISM

OBJECTIVE The autoimmune thyroid diseases, Graves' disease and autoimm une hypothyroidism, result from a complex interaction between genetic, environmental and endogenous factors, The genetic loci conferring sus ceptibility remain unclear. A recent report has demonstrated an associ ation between a microsatellite polymorphism of the CTLA-4 gene (allele 106) on chromosome 2q33 and Graves' disease in Caucasian patients in the USA, The aim of the present study was to confirm this association in UK patients and to determine whether this polymorphism is also asso ciated with autoimmune hypothyroidism. DESIGN Analysis of Caucasian pa tients with autoimmune thyroid disease from a single clinic, compared to local Caucasian controls. PATIENTS We studied 112 patients with Gra ves' disease, 44 with autoimmune hypothyroidism and 91 controls. MEASU REMENTS CTLA-4 microsatellite gene polymorphisms were determined by po lymerase chain reaction amplification of genomic DNA and resolution of the products on sequencing gels. RESULTS As in previous studies, 21 a lleles of the CTLA-4 microsatellite region were detected. Allele 106 w as significantly increased in patients with Graves' disease (P = 0.006 ) and in those with autoimmune hypothyroidism (P = 0.02) when compared to controls. There was no significant difference between the groups i n the distribution of the other alleles and no association between all ele 106 and sex, HLA-DR or -DQ specificities or the presence of ophtha lmopathy in the Graves' patients. CONCLUSIONS These results confirm th at the CTLA-4 gene, or one closely associated with it, confers suscept ibility to Grave's disease but is not specific as the CTLA-4 106 allel e is also associated with autoimmune hypothyroidism. This association seems to be with autoimmune thyroid disease in general.