Unidad de Investigación Médica en Inmunología, Hospital de Pediatría Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Cuauhtémoc 330, Col. Doctores, CP 06720, Ciudad de México, Mexico.
Unidad de Investigación Médica en Enfermedades Infecciosas, Hospital de Pediatría Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Cuauhtémoc 330, Col. Doctores, CP 06720, Ciudad de México, Mexico.
Sci Rep. 2018 Apr 17;8(1):6104. doi: 10.1038/s41598-018-24464-2.
NK cells are important in innate immunity for their capacity to kill infected or cancer cells. The killer cell immunoglobulin-like receptors (KIR) are a family of polymorphic genes with inhibitory and activating functions. The main driving force for gastric cancer (GC) development is a chronic response, which causes an increase of NK cells in the gastric mucosa. The aim of this work was to study polymorphisms in KIR genes in patients with either GC or non-atrophic gastritis (NAG). We studied 242 patients (130 with NAG and 112 with GC) and contrasted with 146 asymptomatic individuals. We analyzed diversity in the content and localization of KIR genes in the different clinical groups studied. Four activating and one inhibitory genes were associated with GC: 2DS1 (OR 3.41), 2DS3 (OR 4.66), 2DS5 (OR 2.25), 3DS1 (OR 3.35) and 2DL5 (OR 3.6). The following were also found as risk factors for GC: Bx genotype (OR 4.2), Bx-Bx centromere-telomere (OR 2.55), cA01|cB03 (OR 36.39) and tB01|tB01 (OR 7.55) gene content and three B motifs (OR 10.9). Polymorphisms in KIR genes were associated with GC and suggest that mutated NK cells may contribute to GC development by increasing gastric mucosa inflammation, leading to constant tissue damage.
自然杀伤 (NK) 细胞在固有免疫中具有杀伤感染或癌细胞的能力,因此十分重要。杀伤细胞免疫球蛋白样受体 (KIR) 是一组具有抑制和激活功能的多态性基因。胃癌 (GC) 发展的主要驱动力是慢性反应,这会导致胃黏膜中 NK 细胞增加。本研究旨在探讨 KIR 基因多态性与 GC 或非萎缩性胃炎 (NAG) 患者的相关性。我们研究了 242 名患者(NAG 组 130 例,GC 组 112 例),并与 146 名无症状个体进行了对比。我们分析了不同临床组中 KIR 基因的含量和定位多样性。有 4 个激活基因和 1 个抑制基因与 GC 相关:2DS1(OR 3.41)、2DS3(OR 4.66)、2DS5(OR 2.25)、3DS1(OR 3.35)和 2DL5(OR 3.6)。以下基因也被认为是 GC 的危险因素:Bx 基因型(OR 4.2)、Bx-Bx 着丝粒-端粒(OR 2.55)、cA01|cB03(OR 36.39)和 tB01|tB01(OR 7.55)基因含量和 3 个 B 基序(OR 10.9)。KIR 基因多态性与 GC 相关,提示突变的 NK 细胞可能通过增加胃黏膜炎症而促进 GC 的发展,从而导致持续的组织损伤。