Department of Gastroenterology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa, Japan.
J Gastrointestin Liver Dis. 2012 Jun;21(2):139-43.
Histamine plays important physiological roles in upper gastrointestinal tract and acts via the H2 receptor. A polymorphism -1018 G>A (rs2067474) was identified in an enhancer element of the HRH2 promoter. We attempted to clarify the associations of this polymorphism with the progression of gastric mucosal atrophy.
Gastric mucosa samples were obtained from 398 subjects with no malignancies. The rs2067474 genotype was determined by PCR-SSCP method. The degree of gastritis was assessed in 366 subjects and serum pepsinogen (PG) I/II levels were measured in 108 subjects. The subjects with atrophy score higher or equal to 2 and metaplasia score higher or equal to1 were classified into the severe atrophic gastritis group (SA group).
The -1018G>A minor allele frequencies in SA and non-SA groups were 8.02% and 13.3%, respectively (p=0.057). The -1018 GG homozygote had a significantly high risk for gastric mucosal atrophy (OR: 2.03, 95%CI: 1.03-4.01, p=0.042). In H. pylori positive subjects, GG homozygote was a more significant risk factor for gastric mucosal atrophy (OR: 2.32, 95%CI: 1.12-4.81, p=0.023). In addition, in the subjects older than 60 years, GG homozygote had also a significant risk for gastric mucosal atrophy (OR: 2.63, 95%CI: 1.15-6.00, p=0.022). In -1018 GG homozygote, PG I/II ratio was significantly lower in H. pylori positive than negative subjects and was significantly decreased with age (p=0.0032 by ANOVA), whereas it was not in the A carrier.
Our results suggest that HRH2 -1018 GG homozygote is a risk factor for the severity of gastric mucosal atrophy under the influence of H. pylori infection, especially in older subjects.
组胺在上消化道中发挥重要的生理作用，通过 H2 受体发挥作用。在 HRH2 启动子的增强子元件中发现了 -1018 G>A（rs2067474）多态性。我们试图阐明该多态性与胃黏膜萎缩进展的关系。
从 398 例无恶性肿瘤的患者中获得胃黏膜标本。采用 PCR-SSCP 法确定 rs2067474 基因型。在 366 例患者中评估胃炎程度，并在 108 例患者中测量血清胃蛋白酶原（PG）I/II 水平。将萎缩评分≥2 分且化生评分≥1 分的患者归入严重萎缩性胃炎组（SA 组）。
SA 组和非 SA 组的-1018G>A 次要等位基因频率分别为 8.02%和 13.3%（p=0.057）。-1018 GG 纯合子发生胃黏膜萎缩的风险显著升高（OR：2.03，95%CI：1.03-4.01，p=0.042）。在 H. pylori 阳性患者中，GG 纯合子是胃黏膜萎缩的更显著危险因素（OR：2.32，95%CI：1.12-4.81，p=0.023）。此外，在年龄大于 60 岁的患者中，GG 纯合子发生胃黏膜萎缩的风险也显著升高（OR：2.63，95%CI：1.15-6.00，p=0.022）。在-1018 GG 纯合子中，H. pylori 阳性患者的 PG I/II 比值明显低于 H. pylori 阴性患者，且随年龄增长而显著降低（方差分析 p=0.0032），而 A 携带者则无此变化。
我们的研究结果表明，HRH2-1018 GG 纯合子是 H. pylori 感染影响下胃黏膜萎缩严重程度的危险因素，尤其是在老年患者中。
