Department of Immunology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
Digestive and General Surgery Service, Principe de Asturias University Hospital, 28015 Madrid, Spain.
Int J Mol Sci. 2024 Oct 3;25(19):10645. doi: 10.3390/ijms251910645.
The Human Leukocyte Antigen (HLA) system contains a set of genes involved at many levels in the innate and adaptive immune response. Among the non-classical HLA class I genes, HLA-G stands out for the numerous studies about its pivotal role in regulating/modulating immune responses. Also, its involvement in extravillous cytotrophoblast function, viral infections, autoimmunity, and cancer has been extensively documented. The present study explores for the first time the relationship between natural alleles of HLA-G, rather than STSs, SNPs, or partial gene polymorphisms, and the development of gastric adenocarcinoma, by analyzing the genetic profile of a cohort of 40 Spanish patients with this type of tumor using DNA extracted from paired biopsies of tumoral and adjacent non-tumoral gastric tissue. Our results reveal a significant statistical relationship between the presence of the allele and the development of gastric cancer, while other common alleles such as or did not demonstrate a significant correlation. Studying the involvement of genes in the development of many diseases is relevant to understanding their pathophysiology. However, the absence of specific mechanisms underlying these associations suggests that investigating complete HLA natural alleles' extended haplotypes or complotypes may offer a more precise and valuable approach to elucidating the association of HLA with the pathogenesis of disease.
人类白细胞抗原 (HLA) 系统包含一组参与固有和适应性免疫反应的多个层次的基因。在非经典 HLA I 类基因中，HLA-G 因其在调节/调节免疫反应方面的关键作用而备受关注。此外，它在绒毛外滋养细胞功能、病毒感染、自身免疫和癌症中的作用也得到了广泛的证实。本研究首次通过分析 40 名西班牙胃腺癌患者肿瘤和相邻非肿瘤胃组织配对活检中提取的 DNA，探讨了 HLA-G 天然等位基因（而非 STS、SNP 或部分基因多态性）与胃腺癌发展之间的关系。我们的研究结果表明，等位基因的存在与胃癌的发生之间存在显著的统计学关系，而其他常见等位基因，如或 ，则没有表现出显著的相关性。研究基因在许多疾病发展中的作用对于理解其病理生理学具有重要意义。然而，这些关联背后缺乏特定的机制表明，研究完整 HLA 天然等位基因的扩展单倍型或 complotype 可能提供一种更精确和有价值的方法来阐明 HLA 与疾病发病机制的关联。
