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Pemphigus foliaceus is an organ-specific autoimmune disease characterized by autoantibodies against the extracellular region of desmoglein 1, a protein that mediates intercellular adhesion in desmosomes. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a key negative regulator of the T cell immune response, playing an important role in T cell homeostasis and maintenance of peripheral tolerance. Polymorphisms in the CTLA4 gene have been associated with autoimmune diseases and the functional CT60 single nucleotide polymorphism (rs3087243, also named 6230G > A) has been proposed to be a casual variant in several of these diseases. The aim of this study was to ascertain whether this polymorphism is associated with inter-individual variation in susceptibility to pemphigus foliaceus. The population sample in this case-control association study comprised 248 patient and 367 controls. We did not found a significant association of pemphigus foliaceus with the CT60 variants. We conclude that the CTLA4CT60 polymorphism is not an important factor for pemphigus foliaceus pathogenesis in the population analyzed.

CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are two receptors that have complementary functions in control of T-cell activation. Polymorphisms of their genes, CD28 and CTLA4, might confer differential susceptibility to diseases resulting from unbalanced or inefficient immune responses. Thus far, little is known about the CD28 polymorphism in populations and even for CTLA4 just one or two single nucleotide polymorphisms (SNPs) are usually analysed. To assess the allelic and haplotypic diversity and linkage disequilibrium in the Brazilian population, two samples differing according to predominant ancestry - African or European - have been analysed for seven SNPs, CD28 -372(G>A), and int3 17(T>C); CTLA4 -1722(T>C), -1577(G>A) -318(C>T), 49(A>G), 6230(G>A) also named CT60, and three microsatellites, CD28 (CAA)n, CTLA4 (AT)n and D2S72 (CA)n. The two population strata show little differentiation, the only significant differences being the allele frequencies of the CTLA4 -1577(G>A) SNP and the CTLA4 (AT)n microsatellite (P = 0.018 and P = 0.007, respectively). Linkage disequilibrium is high, especially between the CTLA4 polymorphisms. However, low r(2) values indicate that none of the markers is a tag SNP in these populations. These results provide valuable information for optimal selection of markers for use in future association studies. We conclude that disease association studies and functional studies addressing the possible consequences of polymorphisms of the 2q33 genomic region should consider haplotypic data besides analysis of individual polymorphisms.

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