Programa de Pós-graduação em Imunologia Básica e Aplicada - PPGIBA, Universidade Federal do Amazonas - UFAM, Brazil.
Cytokine. 2012 Nov;60(2):493-7. doi: 10.1016/j.cyto.2012.04.043. Epub 2012 Jun 8.
Polymorphisms present in the first intron of IFN-γ may have an important role in the regulation of the immune response, which could have functional consequences for gene transcription. Leprosy patients are characterized by different immune responses in different clinical forms. We investigated a possible association of the +874 polymorphism and CA repeats present in the first intron of IFN-γ with susceptibility to leprosy and with the manifestation of the different clinical forms. Nucleotide sequencing was performed with samples from 108 leprosy patients and 113 controls subjects, as well as immunophenotyping of CD(4)(+), CD(8)(+) and CD(69)(+) T cells by flow cytometry. The data showed that there were no significant differences between patients and control subjects, as well as according classification of Ridley-Jopling. However, the A/A genotype was significantly increased in paucibacillary patients (p=0.028) and the microsatellite encoding 16 CA repeats were significantly associated with paucibacillary compared to multibacillary patients (p=0.019). Individuals homozygous for the +874 A allele, the mean level of CD(4)(+) and CD(69)(+) T cells was higher. Our data suggest that polymorphisms present in the first intron of IFN-γ are not associated with susceptibility to leprosy, nevertheless, the +874 polymorphism and the CA repeats number encoded in IFN-γ gene may be related to a higher cellular immune response in patients and are consistently more frequently detected in PB patients.
IFN-γ 第一内含子中的多态性可能在免疫反应的调节中起重要作用,这可能对基因转录具有功能后果。麻风病患者在不同的临床形式中表现出不同的免疫反应。我们研究了 IFN-γ 第一内含子中的+874 多态性和 CA 重复与麻风病易感性以及不同临床形式表现之间的可能关联。对来自 108 例麻风病患者和 113 例对照受试者的样本进行了核苷酸测序,以及通过流式细胞术对 CD(4)(+)、CD(8)(+)和 CD(69)(+)T 细胞进行免疫表型分析。数据显示,患者和对照组之间以及根据 Ridley-Jopling 分类均无显著差异。然而,A/A 基因型在少菌型患者中显著增加(p=0.028),并且编码 16 个 CA 重复的微卫星与少菌型患者相比与多菌型患者显著相关(p=0.019)。+874A 等位基因纯合的个体,CD(4)(+)和 CD(69)(+)T 细胞的平均水平较高。我们的数据表明,IFN-γ 第一内含子中的多态性与麻风病易感性无关,然而,IFN-γ 基因中的+874 多态性和 CA 重复数可能与患者中更高的细胞免疫反应有关,并且在 PB 患者中更频繁地检测到。