Interleukin 1β polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan
Interleukin 1β polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan
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DOI：
10.1053/gast.2002.34156
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发表时间：
2002-07-01
期刊：
影响因子：
29.4
通讯作者：
Sugimurra, H
中科院分区：
文献类型：
--
作者：
Furuta, T;El-Omar, EM;Sugimurra, H
背景与目的：白细胞介素-1 β (il -1 β)多态性与白人胃癌风险增加有关。本研究旨在研究这些多态性对胃酸分泌、萎缩性胃炎和消化性溃疡风险的影响。方法：在单纯胃炎、胃溃疡或十二指肠溃疡（DUs）幽门螺杆菌阳性患者和幽门螺杆菌阴性对照中，检测IL-1B-511/-31和IL-1RN基因型，测定胃液pH、血清胃蛋白酶原（PG） I和11水平，以及胃炎和萎缩评分。结果：在幽门螺杆菌阳性组中，促炎IL-lB-511 T/T基因型患者的萎缩和胃炎评分最高，胃液pH中位数最高，血清PG 1/PG 11中位数最低。IL-1B-511 T/T基因型组随着年龄的增长，胃液pH值显著升高，血清PG I和PG 1/PG 11比值显著降低，但C/C基因型组无年龄依赖性变化。C/T基因型组的变化是中等的。在幽门螺杆菌阴性组中，IL-1位点对任何生理或形态学参数均无影响。携带IL-1RN等位基因2显著保护DU疾病，而il - 1b - 511t /T基因型显著保护60岁以上患者DU复发。结论：在日本，促炎il -1 β多态性与低氯血症和萎缩性胃炎有关。效果取决于幽门螺杆菌感染，并随着年龄的增长而变得更加显著。这也许可以解释日本胃癌的高发病率，以及受感染的受试者中DU复发率的年龄依赖性下降。
Background & Aims: Interieukin-1 beta (IL-1beta) polymorphisms are associated with increased risk of gastric cancer in whites. This study aimed to examine effects of these polymorphisms on gastric acid secretion, atrophic gastritis, and risk of peptic ulcer in Japan. Methods: We determined IL-1B-511/-31 and IL-1RN genotypes and measured gastric juice pH, serum pepsinogen (PG) I and 11 levels, and gastritis and atrophy scores in Helicobacter pylori-positive patients with gastritis only, gastric ulcers, or duodenal ulcers (DUs), and H. pylori-negative controls. Results: In the H. pylori-positive group, subjects with the proinflammatory IL-lB-511 T/T genotype had the highest atrophy and gastritis scores, the highest median gastric juice pH, and the lowest median serum PG 1/PG 11 ratios. Although gastric juice pH significantly increased and serum PG I and PG 1/PG 11 ratios significantly decreased in the IL-1B-511 T/T genotype group with age, no such age-dependent changes were observed in the C/C genotype group. Changes in the C/T genotype group were intermediate. In the H. pylori-negative group, the IL-1 loci had no effect on any of the physiologic or morphologic parameters. Carriage of IL-1RN allele 2 significantly protected against DU disease while the IL-1B-511 T/T genotype significantly protected against DU recurrence in patients older than 60 years. Conclusions: Proinflammatory IL-1beta polymorphisms are associated with hypochlorhydria and atrophic gastritis in Japan. The effects are dependent on H. pylori infection and become more significant with advancing age. This may explain the high incidence of gastric cancer in Japan and also the age-dependent decrease in DU recurrence in infected subjects.