Laboratório de Genética Molecular e Citogenética, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brasil.
Mol Biol Evol. 2011 Nov;28(11):3069-86. doi: 10.1093/molbev/msr138. Epub 2011 May 28.
HLA-G molecule plays an important role on immune response regulation and has been implicated on the inhibition of T and natural killer cell cytolytic function and inhibition of allogeneic T-cell proliferation. Due to its immune-modulator properties, the HLA-G gene expression has been associated with the outcome of allograft and of autoimmune, infectious, and malignant disorders. Several lines of evidence indicate that HLA-G polymorphisms at the 5'-upstream regulatory region (5' URR) and 3'-untranslated region (3' UTR) may influence the HLA-G expression levels. Because Brazilians represent one of the most heterogeneous populations in the world with the widest HLA-G coding region variability already detected among the studied populations, a high level of variability and haplotype diversity would be expected in Brazilians. On this basis, the 5' URR, coding, and 3' UTR variability were evaluated in a Brazilian series consisting of 100 healthy bone marrow donors, as well as the linkage disequilibrium pattern along the gene and the extended haplotypes encompassing several gene segment variations. The HLA-G locus seems to present six different HLA-G lineages showing functional variations mainly in nucleotides of the regulatory regions. Differences were observed at the 5' URR in positions that either coincide with or are close to transcription factor-binding sites and at the 3' UTR mainly in positions that have already been reported to influence HLA-G mRNA availability. We report several lines of evidence for balancing selection acting on the regulatory regions, which may indicate that these HLA-G lineages may be related to the differential HLA-G expression profiles.
HLA-G 分子在免疫反应调节中发挥重要作用，被认为能抑制 T 细胞和自然杀伤细胞的细胞溶解功能，并抑制同种异体 T 细胞的增殖。由于其免疫调节特性，HLA-G 基因的表达与同种异体移植物和自身免疫、感染和恶性疾病的结果有关。有几条证据表明，5' 上游调控区（5' URR）和 3' 非翻译区（3' UTR）的 HLA-G 多态性可能影响 HLA-G 的表达水平。由于巴西人是世界上最多样化的人群之一，在已研究的人群中已经检测到 HLA-G 编码区的最大变异性，因此预计巴西人会有高度的变异性和单倍型多样性。在此基础上，我们评估了一个由 100 名健康骨髓供体组成的巴西系列中的 5' URR、编码和 3' UTR 的变异性，以及基因和包含多个基因片段变异的扩展单倍型的连锁不平衡模式。HLA-G 基因座似乎存在六个不同的 HLA-G 谱系，其功能变化主要发生在调控区的核苷酸上。在 5' URR 位置观察到差异，这些位置要么与转录因子结合位点重合，要么与之接近，而在 3' UTR 位置主要是在已经报道过影响 HLA-G mRNA 可用性的位置。我们报告了几条关于平衡选择作用于调控区的证据，这可能表明这些 HLA-G 谱系与 HLA-G 表达谱的差异有关。
