Analysis of a microsatellite polymorphism of the cytotoxic T-lymphocyte antigen-4 gene in patients with vitiligo

The CTLA-4 gene encodes a T-cell receptor that is involved in the regulatio n of T-cell activation. Recent studies have demonstrated an association of a microsatellite polymorphism [variant lengths of a dinucleotide (AT)(n) re peat] lying in exon 3 of the CTLA-4 gene, specifically a 106-bp allele, wit h autoimmune disorders, such as Graves' disease, autoimmune Addison's disea se and autoimmune hypothyroidism The aim of the present study was to determ ine whether the same polymorphism of the CTLA-4 gene was associated with vi tiligo, a disorder that may have an autoimmune origin and can be present in patients who have one or more autoimmune diseases. CTLA-4 gene microsatell ite polymorphisms were determined for 74 vitiligo patients (53 without any autoimmune disorder; 21 with one or more autoimmune disease) and 173 health y controls, who had no clinical evidence of either vitiligo or any other au toimmune disorder, by polymerase chain reaction amplification of genomic. D NA and resolution of the products on polyacrylamide sequencing gels. The fr equency of the 106-bp allele was significantly increased (chi(2) = 5.2; P = 0.02) in vitiligo patients as a whole, in comparison with control subjects . However, when the patients were classified according to the absence or pr esence of an autoimmune disorder, the frequency of the 106-bp allele was si gnificantly increased (chi(2) = 14.8; P = 0.0001) only in the group of viti ligo patients who also had an autoimmune disease, However, the fact that 17 of 21 patients also had either autoimmune thyroiditis or autoimmune Addiso n's disease probably accounts for the apparent association of vitiligo and the 106-bp allele in this patient group. However, it was found that the rel ative risk of 3.2, conferred by the 106-bp allele in this group of vitiligo patients, was greater than that found for patients with only either Graves ' disease, autoimmune hypothyroidism or autoimmune Addison's disease, with values of 2.1, 2.2 and 2.2, respectively. For the group of patients without an autoimmune disorder, there was no significant difference (chi(2) = 0.2; P = 0.64) in the frequency of the 106-bp allele when compared with control subjects, These results indicate that there is no association between the 106-bp allele and vitiligo, at least when the disorder occurs in the absenc e of an autoimmune disease.