Azuma T, Teramae N, Hayakumo T, Yasuda K, Nakajima M, Kodama T, Inokuchi H, Hayashi K, Taggart R T, Kawai K
Department of Preventive Medicine, Kyoto Prefectural University of Medicine, Japan.
Gut. 1993 Apr;34(4):450-5. doi: 10.1136/gut.34.4.450.
This study was aimed to investigate the association of restriction fragment length polymorphisms (RFLPs) for pepsinogen genes with peptic ulcer disease. Eighty unrelated controls, 61 patients with gastric ulcer, and 57 patients with duodenal ulcer were studied. No genetic polymorphisms for pepsinogen A were detected by EcoRI digestion in Japanese subjects but a 100 base pairs insertion-deletion RFLP for the pepsinogen C gene was observed. The allele frequencies of the large (3.6 kilobase EcoRI fragment) and the small fragment (3.5 kilobase EcoRI fragment) were 80.6% and 19.4% respectively in controls, 55.4% and 44.6% in patients with gastric body ulcer, 79.4% and 20.6% in patients with gastric angular ulcer, 71.4% and 28.6% in patients with gastric antral ulcer, and 75.4% and 24.6% in patients with duodenal ulcer. The allele frequency of the small fragment was significantly higher in patients with gastric body ulcer than in controls and in patients with gastric angular or antral ulcer. The genotypes which possessed the small fragment were significantly more frequent in patients with gastric body ulcer (78.4%) than in controls (33.8%) and in patients with gastric angular or antral ulcer (37.5%). These results suggest that there is a significant association between the genetic polymorphism at the pepsinogen C gene locus and gastric body ulcer, and that the pepsinogen C RFLP is a useful marker of the genetic predisposition to this disorder. These results also indicate genetic heterogeneity of gastric ulcer disease, and suggest that the pepsinogen C RFLP may be a useful subclinical marker to explain the differences in genetic aetiologies of gastric body ulcer and gastric angular or antral ulcer.
本研究旨在探讨胃蛋白酶原基因的限制性片段长度多态性（RFLPs）与消化性溃疡疾病之间的关联。研究了80名无亲缘关系的对照者、61名胃溃疡患者和57名十二指肠溃疡患者。在日本受试者中，经EcoRI酶切未检测到胃蛋白酶原A的基因多态性，但观察到胃蛋白酶原C基因存在100个碱基对的插入 - 缺失RFLP。在对照者中，大片段（3.6千碱基EcoRI片段）和小片段（3.5千碱基EcoRI片段）的等位基因频率分别为80.6%和19.4%；在胃体部溃疡患者中分别为55.4%和44.6%；在胃角部溃疡患者中分别为79.4%和20.6%；在胃窦部溃疡患者中分别为71.4%和28.6%；在十二指肠溃疡患者中分别为75.4%和24.6%。胃体部溃疡患者中小片段的等位基因频率显著高于对照者以及胃角部或胃窦部溃疡患者。拥有小片段的基因型在胃体部溃疡患者（78.4%）中比对照者（33.8%）以及胃角部或胃窦部溃疡患者（37.5%）中更为常见。这些结果表明，胃蛋白酶原C基因位点的基因多态性与胃体部溃疡之间存在显著关联，并且胃蛋白酶原C RFLP是该疾病遗传易感性的一个有用标志物。这些结果还表明胃溃疡疾病存在遗传异质性，并提示胃蛋白酶原C RFLP可能是一个有用的亚临床标志物，可用于解释胃体部溃疡与胃角部或胃窦部溃疡遗传病因的差异。
