Pavoni D P, Cerqueira L B, Roxo V M M S, Petzl-Erler M L
Laboratório de Genética Molecular Humana, Universidade Federal do Paraná, Curitiba, PR, Brasil.
Braz J Med Biol Res. 2006 Sep;39(9):1227-32. doi: 10.1590/s0100-879x2006000900010.
Endemic pemphigus foliaceus (EPF) is an autoimmune bullous skin disease characterized by acantholysis and antibodies against a desmosomal protein, desmoglein 1. Genetic and environmental factors contribute to development of this multifactorial disease. HLA class II and some cytokine gene polymorphisms are the only genetic markers thus far known to be associated with susceptibility to or protection from EPF. The cytotoxic T-lymphocyte antigen-4 gene (CTLA4) encodes a key immunoreceptor molecule that regulates and inhibits T-cell proliferation. It participates in the regulatory process controlling autoreactivity and therefore has been considered a strong candidate gene in autoimmune diseases. In the search for genes that might influence EPF pathogenesis, we analyzed variants of the CTLA4 gene in a sample of 118 patients and 291 controls from a Brazilian population. This is the first study investigating the possible role of polymorphisms of the 2q33 chromosomal region in differential susceptibility to pemphigus foliaceus. Promoter region and exon 1 single nucleotide polymorphisms -318 (C,T) and 49 (A,G) were genotyped using sequence-specific oligonucleotide probes after amplification by the polymerase chain reaction. The allelic and genotypic frequencies did not differ significantly between the patient and the control groups (-318T: 9.8 and 10.9%, 49G: 33.0 and 35.2% were the allelic frequencies in patients and controls, respectively). In addition, no significant difference was found when the patient and control population samples were stratified by the presence of HLA-DRB1 alleles. We conclude that the CTLA4 -318 (C,T) and 49 (A,G) polymorphisms do not play a major role in EPF development.
地方性落叶型天疱疮（EPF）是一种自身免疫性大疱性皮肤病，其特征为棘层松解以及存在针对桥粒蛋白桥粒芯糖蛋白1的抗体。遗传和环境因素促成了这种多因素疾病的发生。HLA II类分子和一些细胞因子基因多态性是目前已知的仅有的与EPF易感性或保护性相关的遗传标记。细胞毒性T淋巴细胞抗原4基因（CTLA4）编码一种关键的免疫受体分子，该分子调节并抑制T细胞增殖。它参与控制自身反应性的调节过程，因此被认为是自身免疫性疾病中一个强有力的候选基因。在寻找可能影响EPF发病机制的基因时，我们分析了来自巴西人群的118例患者和291例对照样本中CTLA4基因的变异。这是第一项研究2q33染色体区域多态性在落叶型天疱疮易感性差异中可能作用的研究。通过聚合酶链反应扩增后，使用序列特异性寡核苷酸探针，对启动子区域和外显子1单核苷酸多态性-318（C，T）和49（A，G）进行基因分型。患者组和对照组之间的等位基因和基因型频率无显著差异（-318T：患者和对照组的等位基因频率分别为9.8%和10.9%，49G：分别为33.0%和35.2%）。此外，当根据HLA-DRB1等位基因的存在情况对患者和对照人群样本进行分层时，未发现显著差异。我们得出结论，CTLA4 -318（C，T）和49（A，G）多态性在EPF的发生中不发挥主要作用。
