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The major- and trace-element compositions of amphiboles in andesite from Quaternary Yufu Volcano, northeastern Kyushu, Japan were analysed to investigate the generation processes of andesitic magma from Yufu Volcano. The amphiboles in andesite from Yufu volcano can be divided into two groups based on major-element composition: pargasite and magnesio-hornblende. To estimate temperature, pressure, and major- and trace-element compositions of melts in equilibrium with amphiboles, we used the recently proposed methods that can calculate temperature, pressure, major element compositions, and partition coefficients of trace-element between amphibole and melt using only the major-element compositions of amphibole. The estimated temperature, pressure, and major-element composition of melt in equilibrium with the amphibole phenocrysts indicate that each group crystallised under different conditions. These differences suggest that two magma chambers at different depths existed beneath Yufu Volcano and that the andesitic magma of Yufu Volcano was formed by mixing of the two magmas. The trace-element compositions of melts in equilibrium with the pargasite and magnesio-hornblende, estimated by applying the partition coefficients calculated from major-element compositions of amphibole to trace-element compositions of amphiboles, indicate magma derived from slab melt and the partial melting of crustal material, respectively. Because magma is a mixture of minerals and melt, we estimate the chemical compositional ranges of the two end-member magmas on the Y versus SiO2 diagram from the mixing relationship between amphibole and estimated melt, as well as phenocrysts of plagioclase, clinopyroxene, and orthopyroxene. The overlap of the estimated compositional range with the trend of whole-rock composition represents the chemical compositions of the end-members of magma mixing, yielding estimates of the mafic (SiO2 ≈ 45 wt %) and felsic (SiO2 ≈ 68 wt %) end-member magmas. Furthermore, we estimate the concentrations of other elements in the end-member magmas by substituting the estimated SiO2 concentrations of the magmas into linear regression equations between the whole-rock contents of other elements and SiO2. The trace-element compositions of the mafic and felsic end-member magmas, as estimated in this study, have similar features to those of gabbroids and Cretaceous granitic rocks, respectively, that are presumed to lie beneath Yufu Volcano. These similarities could be explained by the possibility that the compositions of the end-member magmas were influenced by basement rocks. [ABSTRACT FROM AUTHOR]

Background and Aim: In colorectal endoscopic submucosal dissection (ESD), post‐ESD electrocoagulation syndrome (PECS) has been recognized as one of the major complications. There are no reports on the relationships between ESD findings and PECS. This study aims to evaluate the risk factors for PECS, including ESD findings such as muscularis propria exposure. Methods: We performed a retrospective cohort study of patients who underwent colorectal ESD between January 2017 and December 2021 in Japan. The grade of injury to the muscle layer caused by ESD was categorized as follows: Grade 0, no exposure of muscularis propria; Grade 1, muscularis propria exposure; Grade 2, torn muscularis propria; and Grade 3, colon perforation. The risk factors for PECS, including injury to the muscle layer, were analyzed by univariate and multivariate analyses. Results: Out of 314 patients who underwent colorectal ESD, PECS occurred in 28 patients (8.9%). The multivariate analysis showed that female sex (odds ratio [OR] 3.233; 95% confidence interval [95% CI]: 1.264–8.265, P = 0.014), large specimen size (≥ 40 mm) (OR 6.138; 95% CI: 1.317–28.596, P = 0.021), long procedure time (≥ 90 min) (OR 2.664; 95% CI: 1.053–6.742, P = 0.039), and Grade 1 or 2 injury to the muscle layer (OR 3.850; 95% CI: 1.090–13.61, P = 0.036) were independent risk factors for PECS. Conclusions: Injury to the muscle layer, such as exposure or tear, was identified as a novel independent risk factor for PECS. We should perform colorectal ESD carefully to avoid injuring the muscle layers. [ABSTRACT FROM AUTHOR]

Geochronological and geochemical studies reveal the possible origin of the restricted body of mylonite rocks occurring at the eastern edge of Kyushu Island, Japan, just in contact with the Sashu Fault, a part of the Paleo‐Median Tectonic Line (Paleo‐MTL). The LA‐ICP‐MS zircon U–Pb dating of the quartz diorite mylonite in this mylonitic body indicates a crystallization age of 114.0 ±1.7 Ma. Moreover, the two tonalite samples appear as thin layers within the Permian fine‐grained mafic mylonite; a part of the same body yields the age of 113.7 ±2.3 Ma and 116.9 ±1.3 Ma, with extremely low Th/U ratio. These quartz diorite mylonite and tonalite are consistent with the late Early Cretaceous magmatism and coeval metamorphism similar to those in the Higo Plutono‐metamorphic Complex in western Kyushu, Japan. This newly characterized complex occurs just south of the Cretaceous Sambagawa metamorphic rocks. The newly characterized mylonitic rocks are lying structurally above the Sambagawa Metamorphic Complex and are distributed along the Paleo‐MTL. The extension of the Higo Plutonometamorphic Complex, as well as the structural relationship between this complex and the Sambagawa Metamorphic Complex, is still controversial but holds a key to reconstruct the tectonic evolution of Southwest Japan during the Late Mesozoic to Early Cenozoic period. Hence, this article provides new insight into the reconstruction of the evolution history of East Asia as an active convergent margin. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate whether single nucleotide polymorphisms in the DNMT3A gene are associated with susceptibility to gastric cancer in the Japanese population. The present case-control study examined the associations between single nucleotide polymorphisms (rs6733868 and rs13428812) in DNMT3A and cancer susceptibility in 343 patients with gastric cancer and 708 subjects without gastric malignancies on upper gastro-duodenal endoscopy. Of 708 controls, 409 were classified into two groups histologically: 99 cases with and 310 cases without gastric mucosal atrophy. Overall, homozygosity for the DNMT3A rs6733868 minor allele was significantly associated with a reduced risk of gastric cancer (odds ratio [OR], 0.621; 95% confidence interval [CI], 0.402–0.958; P=0.031), especially of the intestinal type (OR, 0.494; 95% CI, 0.274–0.890; P=0.019). In subjects >60 years, rs6733868 minor allele homozygosity was significantly associated with gastric cancer susceptibility. Carriers of the rs6733868 minor allele had a reduced risk of severe gastric mucosal atrophy (OR, 0.495; 95% CI, 0.299–0.826; P=0.0069). In addition, the number of minor alleles of both rs6733868 and rs13428812 was significantly correlated with the risk of Helicobacter pylori (HP) infection (P=0.0070 and P=0.0050, respectively). However, rs13428812 was not associated with severe gastric mucosal atrophy or gastric carcinogenesis. The present results suggest that DNMT3A polymorphisms serve roles in the progression from HP infection to gastric mucosal atrophy and gastric carcinogenesis in terms of degree and manner. [ABSTRACT FROM AUTHOR]

Background and Aims: Fusobacterium species are part of the gut microbiome in humans, but some species have been recognized as opportunistic pathogens implicated in inflammatory diseases including inflammatory bowel diseases. Here, we performed prevalence screening of Fusobacterium in ulcerative colitis (UC) in Japanese patients. Methods: We examined Fusobacterium nucleatum ( F. nucleatum) and whole Fusobacterium species ( Pan- fusobacterium) by quantitative real-time PCR in 163 inflamed mucosae from 152 UC patients. Data were correlated with clinical subtypes of UC. Results: In an initial prevalence screen, F. nucleatum and Pan- fusobacterium were detected in 6.3 % (4/64) and 53.1 % (34/64). For all 163 mucosae, the prevalence of Pan- fusobacterium was 54.6 % (89/163). Pan- fusobacterium status was concordant in inflamed and normal adjacent samples, and the matched cases during 1-year follow-up colonoscopy. The higher amount of Pan- fusobacterium was observed in chronic continuous type compared to one attack and relapse/remitting type ( p = 0.039). The higher amount of Pan- fusobacterium was also associated with rather mild clinical course of disease, such as non-steroid dependency ( p = 0.015), non-refractory phenotype ( p = 0.013), and non-severe phenotype ( p = 0.04). Based on the distribution of Pan- fusobacterium measurable cases, we identified 10 cases as having a high amount of Pan- fusobacterium (FB-high). The clinicopathological features of FB-high UC cases were also highlighted by chronic continuous type and mild phenotypes of disease. Conclusion: Whole Fusobacterium species, but not F. nucleatum, are common in UC patients and have a role in persistence of colonic inflammation in UC. However, Fusobacterium infection is associated with rather mild clinical phenotypes of UC. [ABSTRACT FROM AUTHOR]

Behavior of zircon at the schist/migmatite transition is investigated. Syn-metamorphic overgrowth is rare in zircon in schists, whereas zircon in migmatites has rims with low Th/U that give 90.3 ± 2.2 Ma U-Pb concordia age. Between inherited core and the metamorphic rim, a thin, dark-CL annulus containing melt inclusion is commonly developed, suggesting that it formed contemporaneous with the rim in the presence of melt. In diatexites, the annulus is further truncated by the brighter-CL overgrowth, suggesting the resorption and regrowth of the zircon after near-peak metamorphism. Part of the zircon rim crystallized during the solidification of the melt in migmatites. Preservation of angular-shaped inherited core of 5-10 μm in zircon included in garnet suggests that zircon of this size did not experience resorption but developed overgrowths during near-peak metamorphism. The Ostwald ripening process consuming zircon less than 5-10 μm is required to form new overgrowths. Curved crystal size distribution pattern for fine-grained zircons in a diatexite sample may indicate the contribution of this process. Zircon less than 20 μm is confirmed to be an important sink of Zr in metatexites, and ca. 35-μm zircon without detrital core are common in diatexites, supporting new nucleation of zircon in migmatites. In the Ryoke metamorphic belt at the Aoyama area, monazite from migmatites records the prograde growth age of 96.5 ± 1.9 Ma. Using the difference of growth timing of monazite and zircon, the duration of metamorphism higher than the amphibolite facies grade is estimated to be ca. 6 Myr. [ABSTRACT FROM AUTHOR]

Background: The role of genetics in the susceptibility to functional dyspepsia (FD) remains unclear. We attempted to clarify the association between FD and polymorphisms in SLC6A4. In addition, rs5981521 (C>T) in the pri-microRNA 325 (pri-miR-325) coding region was also investigated. Methods: The study was performed in 395 subjects (172 with no upper abdominal symptoms and 223 with FD, including medication-resistant FD). We employed a polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method to detect gene polymorphisms. Results: Neither SLC6A4 −185 A>C nor *463 G>T was associated with susceptibility to FD. The number of rs5981521 T alleles was significantly correlated with an increased risk for FD (odds ratio [OR] 1.45, 95 % confidence interval [CI] 1.05-1.98; p = 0.022) and the TT homozygote was more closely associated with the risk for FD (OR 3.01, 95 % CI 1.41-6.42; p = 0.0043). The TT homozygote also had significantly increased risks for both the epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) subtypes of FD (OR 3.04, 95 % CI 1.25-7.42; p = 0.014 and OR 3.05, 95 % CI 1.14-8.13; p = 0.026, respectively). In addition, Helicobacter pylori-negative TT homozygotes had a greater risk for FD (OR 8.37, 95 % CI 1.78-39.5; p = 0.0072). In subjects with the SLC6A4 5′-untranslated region (UTR) wild homozygote, the number of rs5981521 T alleles was significantly correlated to an increased risk for FD (OR 1.45, 95 % CI 1.03-2.04, p = 0.033). Of note, in subjects who were SLC6A4 3′-UTR mutant carriers, the number of rs5981521 T alleles was also significantly correlated with an increased risk for FD (OR 2.07, 95 % CI 1.08-3.98; p = 0.029). Conclusions: Our results suggest that the genetic polymorphism pri-miR-325 is associated with FD and interacts with SLC6A4 polymorphisms in increasing susceptibility to FD in Japanese. [ABSTRACT FROM AUTHOR]

The compounded impacts of the catastrophes that resulted from the Great East Japan Earthquake have emphasized the need to develop strategies to respond to multiple types and sources of contamination. In Japan, earthquake and tsunami-generated waste were found to have elevated levels of metals/metalloids (e.g., mercury, arsenic, and lead) with separation and sorting more difficult for tsunami-generated waste as opposed to earthquake-generated waste. Radiation contamination super- imposed on these disaster wastes has made it particularly difficult to manage the ultimate disposal resulting in delays in waste management. Work is needed to develop policies a priori for handling wastes from combined catastrophes such as those recently observed in Japan. [ABSTRACT FROM AUTHOR]

Host genetic factors may play a key role in determining the long-term outcome of the Helicobacter pylori infection. Toll-like receptor 4 (TLR4) and CD14-mediated recognition of lipo-polysaccharide (LPS) is required for efficient recognition of gram-negative bacterial infections. We investigated the effects of common polymorphisms of TLR4 Asp299Gly, Thr399Ile, and CD14 promoter-C159T on the risk of gastric cancer including its subtypes and clinicopathologic features. We also investigated the effects of these polymorphisms on histologic degree of H. pylori-induced gastritis. The study was performed in 149 gastric cancer (GC) cases [mean age 64.0 +/- 12.4, M:F = 109:40] and 94 patients without evidence of GC (mean age 64.1 +/- 12.3, M:F = 65:25, Peptic ulcer diseases = 43.6%, gastritis = 56.4%) as the control group. TLR4 Asp299Gly, Thr399Ile, and CD14 promoter-C159T were determined by PCR-RFLP in all the patients. Gastritis scores of non-cancerous gastric mucosa were assessed according to the updated Sydney system in H. pylori-positive subjects (n = 179). The frequencies of CD14-260 TT and T carrier were significantly lower in patents with intestinal-type gastric cancer than in controls (OR = 0.31; 95%CI = 0.12-0.78, OR = 0.38; 95%CI = 0.18-0.81, respectively). Compared to patients older than 61 years, the atrophy score in antrum was significantly lower in TT and CT patients. TLR4 Asp299Gly and Thr399Ile were not detected in all the patients. Our data suggests that CD14 promoter-159TT and T carrier were associated with a lower risk of developing gastric mucosal atrophy in H. pylori-infected patients of more than 61 years of age, and these genotypes may reduce the risk of intestinal-type gastric cancer. [ABSTRACT FROM AUTHOR]

Objective. Superoxide has been implicated in the pathogenesis of Helicobacter pylori-related diseases through inflammation. NADPH oxidase, a major source of superoxide generation, plays a critical role in H. pylori-related gastric inflammation. The aim of this study was to clarify the effect of the p22PHOX C242T polymorphism, an essential component of NADPH oxidase in the risk of gastroduodenal diseases, on the severity of H. pylori-induced gastritis in a Japanese population. Material and methods. The study comprised 436 patients attending the Endoscopy Center of Fujita Health University Hospital. The p22PHOX C242T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system. Results. The 436 patients represented 106 gastric ulcers (24.3%), 48 duodenal ulcers (11.0%), and 282 non-ulcer subjects (64.7%). No association was found between p22PHOX polymorphism and the risk of ulcer diseases compared to non-ulcer subjects. However, among H. pylori-positive subjects, the degree of intestinal metaplasia tended to be lower in 242T carriers aged more than 60 years (p=0.0488). The same allele also decreased the risk of developing a more severe intestinal metaplasia in H. pylori-positive female subjects (p=0.0441). Conclusions. Our data suggest that the p22PHOX 242T allele is associated with a reduced risk of developing a more severe intestinal metaplasia in subjects older than 60 years of age and in female subjects with H. pylori infection. [ABSTRACT FROM AUTHOR]

Background: Mannan-binding lectin (MBL) is believed to be an important constituent of the innate immune system. It has been reported that the codon 54 G/A polymorphism of exon-1 affects the MBL2 gene and alters its activity.Aims: We investigated the association between polymorphism of the MBL2 gene and gastric cancer risk as well as Helicobacter pylori infection in a Japanese population.Methods: The study cohort comprised 388 gastric cancer patients and 144 healthy volunteers. Polymorphism at codon 54 of exon 1 of the MBL2 gene was investigated by PCR-based restriction fragment length polymorphism analysis.Results: There was no significant difference in the distribution of the MBL2 genotype among the gastric cancer patients and healthy controls. However, the carrier of the A allele was more prevalent among patients with a more advanced stage gastric cancer [odds ratio (OR) 1.68, 95% confidence interval (CI) 1.05-2.67; P = 0.03] and also had an increased risk of gastric cancer among patients 65 years of age or younger (OR = 1.6, 95%CI = 1.01-2.52, <0.05).Conclusion: The codon 54 polymorphism of the MBL2 gene is associated with more advanced phenotypes of gastric cancer and the risk of gastric cancer in Japanese patients 65 years of age or younger. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) play important roles in the signaling of many pathogen-related molecules and endogenous proteins associated with immune activation. -196 to -174del polymorphism affects the TLR2 gene and alters its promoter activity. We investigated the influence of TLR2 -196 to -174del polymorphism on the risk of gastro-duodenal diseases, on the severity of Helicobacter pylori-induced gastritis in a Japanese population. The study was performed on 309 patients with abdominal discomfort and 146 healthy controls. -196 to -174del polymorphism of TLR2 was investigated by allele-specific polymerase chain reaction method in all of the subjects. Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system in H. pylori-positive subjects (n = 156). Patients with abdominal discomfort was consisted of 80 gastric ulcers (25.9%), 38 duodenal ulcers (12.3%), five gastric + duodenal ulcers (1.6%), 105 patients with gastritis (34.0%) and 81 normal healthy stomachs (26.2%). We did not find any association between TLR2 polymorphism and risk of gastric ulcer, duodenal ulcer, gastric and duodenal ulcer and gastritis compared to healthy controls. However, the TLR2-196 to -174ins allele was associated with severity of intestinal metaplasia in more than 60 years of ages (P = 0.02). The same allele also increased the risks of developing more severe gastric mucosal atrophy and intestinal metaplasia in female subjects (P < 0.05, P = 0.07 respectively). No association was observed between TLR2 polymorphism and severity of neutrophil and mononuclear cell infiltration. Our data suggest that the TLR2-196 to -174ins allele was associated with more severe intestinal metaplasia in patients older than was correlated with severity of gastric mucosal atrophy and intestinal metaplasia in female subjects. [ABSTRACT FROM AUTHOR]

Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to inhibit the proliferation of gastric cancer cells. A common polymorphism at codon 12 of this gene (Pro12Ala) has been shown to confer protection against diabetes and colorectal cancer. We investigated the influence of PPARgamma gene Plo12Ala polymorphism on the risk of gastric cancer and on the severity of Helicobacter pylori-induced gastritis as well as impaired fasting glucose (IFG) in Japanese. About 215 patients with gastric cancer (GC) and 201 patients without GC enrolled in this study. Plo12Ala polymorphism of PPARgamma was investigated by PCR-RFLP in all of the subjects. The gastritis score of noncancerous antral mucosa was calculated by the updated Sydney system. The diagnosis of IFG was based on repeated evidence of serum fasting glucose (SFG) concentration of greater than or equal to 110 mg/dl. The Plo12Ala genotype of PPARgamma showed a significantly higher frequency in GC patients than in controls (OR = 2.43; 95%CI = 1.04-5.67). In contrast, the Plo12Ala genotype held a lower risk of IFG (OR = 0.33; 95%CI = 0.13-0.83). The same genotype was associated with an increased risk of non-cardiac gastric cancer (OR = 2.39; 95%CI = 1.02-5.65), lower third gastric cancer (OR = 3.56; 95%CI = 1.31-9.71), advanced cancer (OR = 2.93; 95%CI = 1.13-7.58), and Lauren's intestinal cancer (OR = 2.94; 95%CI = 1.13-7.66). Among 151 gastric cancer subjects, the atrophy and metaplasia scores of the antral mucosa adjacent to cancer showed a tendency to be higher in those with the 12Ala allele. Our study suggests that the PPARgamma Pro12Ala polymorphism may be a shared risk marker of both IFG and gastric cancer in Japanese. [ABSTRACT FROM AUTHOR]

The role of genetics in the susceptibility to functional dyspepsia (FD) is not well established. Recently, two different associations were reported between FD and G-protein beta3 (GNB3) subunit gene polymorphism. We aim to clarify the association between GNB3 protein C825T polymorphism and dyspepsia in the Japanese population. Eight-nine dyspeptics and 94 nondyspeptic subjects enrolled in this study. All subjects underwent gastroscopy and patients with significant upper gastrointestinal findings were excluded. Other diseases were also excluded by face-to-face history and physical examination. GNB3 protein C825T polymorphisms were determined by polymerase chain reaction-restriction fragment-length polymorphism. H. pylori infection status was examined by histology or antibody against H. pylori. Nonsignificant correlation was found between GNB3 protein homozygous 825T and unexplained dyspepsia (OR = 1.65, 95% CI: 0.87-3.13). However, among H. pylori-negative subjects, homozygous GNB3 protein 825T significantly increased the risk of dyspepsia (16.7% versus 40.5%; CC versus TT; OR = 5.10, 95% CI: 1.21-21.43, CC versus others; OR = 3.40, 95% CI: 1.16-9.93, respectively). This significant association remained after logistic regression analysis with adjustment for sex and age (CC versus TT; OR = 5.73, 95% CI: 1.27-25.82, CC versus others; OR = 3.08, 95% CI: 1.02-9.25). No significant correlation was found between GNB3 polymorphism and any dyspeptic symptoms. Our data suggest that the homozygous 825T allele of GNB3 protein is associated with dyspepsia in the H. pylori-negative Japanese population. The role of genetics in the development of dyspepsia needs further evaluation. [ABSTRACT FROM AUTHOR]

The Mesozoic geological history of proto-Japan holds a crucial role in understanding the tectonic evolution during this time in East Asia, as a whole. In this context, the evolutionary history of the Median Tectonic Line (MTL) is important but still under debate. Most of the studies on the MTL were carried out on well-preserved clear zonally distributed areas such as the central Shikoku Island, Southwest Japan. However, these clear zonal arrangements are absent and several tectonic units including the MTL appear in close proximity at the westernmost Shikoku Island and the Maana Belt occurs here in a restricted area. Such unclear arrangements of lithounits pose a difficulty for a comprehensive understanding of the large-scale tectonic evolution of Southwest Japan. Hence, the study on and along the Maana Belt is crucial to unravel the holistic tectonic evolution of the MTL. The zircon age dating of the tonalites, geochemically of volcanic arc affinity, revealed 470.6 ± 3.2 and 468.3 ± 2.7 Ma as a magmatic age, which confirmed them as members of the Kurosegawa tectonic zone. In contrast, the scarce chemically-altered leucocratic mylonite shows the zircon age of 151.8 ± 1.8 Ma as a possible timing of magmatism. This may be the exotic block because its age is known as a magmatic hiatus in Southwest Japan. The detrital zircon dating of three (meta-)sedimentary rocks along the Maana Belt confirmed that they can be attributed to the Northern Chichibu Belt or the Kurosegawa tectonic zone. Newly characterized rock unit (= the Northern Chichibu Belt with the Kurosegawa tectonic zone) is in contact with the mid-Cretaceous igneous province of the Oshima metamorphic rocks. The suggested juxtaposition in the present study area is a remnant of the original settings including the initial phase of the MTL but is completely disrupted by the exhumation of the Sambagawa Belt in major parts of the Shikoku Island. Identifying this original setting provides not only the initial arrangement of different lithounits but also a clear understanding of the preexisting large-scale tectonic modification systems at the margin of the East Asian continent. [Display omitted] • Precise distribution of particular terranes in western shikoku was revealed. • Terrane alignment at the latest Cretaceous in Southwest Japan was revealed. • Sinistral faulting stage MTL was disappeared by the exhumation of Sambagawa Belt. • Large scale strike-slip fault occurred at most oceanic side of the East Asia. [ABSTRACT FROM AUTHOR]

Aso volcano has the largest caldera (18 × 25 km in diameter) in the southwestern Japan Island Arc, and it formed as the result of four large (VEI = 6–7) pyroclastic-eruption cycles. We study the penultimate large eruption cycle, the Aso-3 cycle, which occurred 123 ka with an ejecta volume of more than 150 km 3 . The processes in the pre-eruptive magma chamber and the magma genesis of the Aso-3 cycle were inferred from geological data, phenocryst chemistry, and whole-rock chemical and Sr-, Nd-, and Pb isotopic analyses of juvenile clasts. The geological and petrological data indicate that the pre-eruptive magma chamber was stratified compositionally into three layers: from top to bottom, silicic, intermediate, and mafic magma layers. The three magma layers had a uniform isotope composition, suggesting that all the magmas were generated from a single source. The silicic and intermediate magmas were not generated from the mafic magma by fractional crystallization. The silicic magma has higher Ni content (compatible element) than the mafic magma. This suggests that these magmas were produced by partial melting of the same mafic crust but with differing amounts of partial melting: the silicic magma was produced by a low degree of partial melting of the source rock without fractional crystallization, and the mafic magma was produced by a large degree of partial melting followed by fractional crystallization. The intermediate magma compositions plot on the tie line between the silicic magma and the melt of the mafic magma in variation diagrams, and the intermediate magma has phenocrysts whose compositions are identical with those in the silicic magma. This observation indicates that, before the Aso-3 eruption cycle, a two-layer stratified magma chamber of the silicic and mafic magmas was formed as a result of melting of the mafic crust, which was followed by formation of the intermediate layer as a result of interfacial mixing between the silicic magma and the melt of mafic magma. During the eruption the three-layer stratified magma chamber was tapped from the top to the bottom. [ABSTRACT FROM AUTHOR]

Abstract: Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator. Two functional polymorphisms were identified in the promoter region of MIF gene. We attempted to clarify the associations between these polymorphisms and ulcerative colitis (UC). The study was performed in 111 patients with UC and 209 subjects without UC. We employed the PCR–SSCP method to detect gene polymorphisms. Overall, 5/5-CATT genotype was a decreased risk for the development of UC (OR, 0.51; 95% CI, 0.26–0.99). In addition, 7/7-CATT genotype was significantly associated with chronic continuous phenotype and distal colitis phenotype (OR, 5.49; 95% CI, 1.19–25.3, and OR, 6.10; 95% CI, 1.32–28.2, respectively), whereas 5/5-CATT genotype had an inhibitory effect on the development of UC after 20years of age (OR, 0.33; 95% CI, 0.14–0.82). On the other hand, G-173C polymorphism did not affect the susceptibility to and the phenotypes of UC. Our results suggested that tetranucleotide CATT repeat of MIF gene promoter may be associated with the development of UC and the severity of inflammation in patients with UC. [Copyright &y& Elsevier]

• Tsuwano Complex forms the westernmost end of the Permian Maizuru Terrane, Japan. • This newly discovered basement rock complex formed between ca. 2.7 Ga and 1.85 Ga. • Early volcanic arc related granitic crust was formed between ca. 2.7 Ga and 2.5 Ga. • Coeval granitoid magmatism and metamorphism occurred at ca. 1.85 Ga. • Deep to shallow crust (quartzite <2.4 Ga) correlates to Asian continental neighbors. A new rock complex has been discovered from the Tsuwano area of Southwest Japan. This granitic rock complex namely, Tsuwano Complex contains foliated granitic gneiss, massive granitoids, and metaquartzite, forming a distinct unit at the westernmost end of the east-west elongate Maizuru Terrane. The above-mentioned litho-assemblage is characteristically different in appearance from the typical rocks of the Maizuru Terrane as well as the surrounding Jurassic and Permian accretionary rocks. We report here the zircon U-Pb LA-ICP-MS geochronological data of the rocks of this Tsuwano Complex. The comprehensive geochronological data indicate that this complex is much older than the surrounding rocks of the Maizuru Terrane. Zircon cores of the granitic gneiss yield possible magmatic age at ca. 2700 and 2500 Ma, while rim parts show a possible metamorphic age of ca. 1850 Ma. Associated dioritic to tonalitic granitoids also show a comparable age of crystallization at ca. 1850 Ma, indicating Neoarchean granitic rocks suffering a thermal overprinting and associated granitoid magmatism at Paleoproterozoic era. The exposed metaquartzite also yielded Neoarchean detrital zircon grains with the calculated maximum age of deposition at ca. 2430 Ma. While, all the other studied rocks including the grayish granitoids, felsic tuff, and metagabbro yield Paleozoic to Mesozoic ages. This is the first discovery of a Precambrian basement rock complex from the Japanese main islands. Based on the present geochronological dataset, we propose for a correlation and paleo-positioning of these basement rocks on the East Asian cratonic margin and a possible tectonic model of its evolution. [ABSTRACT FROM AUTHOR]

Background & Aims: We aimed to establish a comorbidity index for small bowel vascular diseases (SBVD) associated with small bowel bleeding (SBB) and recurrent bleeding., Methods: We performed a retrospective analysis of 404 patients diagnosed with SBB via double-balloon enteroscopy, at 2 hospitals in Japan from June 2003 through July 2016. We collected data on comorbidities, computed Charlson Comorbidity Index and anticoagulation and risk factors in atrial fibrillation (ATRIA) scores, and analyzed associations with SBVD, rebleeding, and overall survival associated with bleeding and/or comorbidities. We used these data to develop a comorbidity index to identify patients at risk for SBVD, rebleeding, and reduced survival time. We validated our findings in a separate, prospective cohort of 88 patients with SBB., Results: We developed a weighted index (the Ohmiya index) that identified patients who developed SBVD with an area under the receiver operating characteristic (AUROC) curve of 0.7758; this value was higher than that of the Charlson index score (0.6828; P < .0001) or ATRIA score (0.6728; P < .0001) alone. Among the 51 patients taking oral anticoagulants, there was no significant difference in AUROCs for the Ohmiya score (0.5254) vs the outcomes registry for better informed treatment score (0.5857; P = .4300). In the retrospective cohort, the Ohmiya index identified patients with SBVD with 68% sensitivity (93/137), 84% specificity (223/267), and 78% accuracy (316/404); in the validation cohort, these values were 63% (22/35), 85% (45/53), and 76% (67/88), respectively. Onset age <50 years and index score <2 identified patients with Meckel's diverticulum and Crohn's disease with 53% accuracy. Onset age ≥50 years and index score <2 identified patients with inflammatory diseases, drug-induced injuries, or tumors with 72% accuracy. An index score ≥2 identified patients with SBVD with 68% accuracy, regardless of age. Among patients with Ohmiya index scores ≥2, 33% had rebleeding; among patients with scores <2, 15% had rebleeding (hazard ratio for score ≥2, 1.729; 95% CI, 1.038-2.882; P = .0355)., Conclusion: We developed an index, based on comorbidities and age of onset of SBB, that identified patients at risk for rebleeding and vascular disease (for example, enteroscopic hemostasis for SBVD, medication for inflammatory diseases, surgery with enteroscopic tattooing for tumors and diverticula). UMIN: 000025693., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Visceral sensory impulses are transmitted via C-fibers from the gastrointestinal tract to the central nervous system. The tetrodotoxinresistant (TTX-r) sodium channel, Na(V) 1.8/SNS (sensory-neuron specific), encoded by SCN10A, has been identified on C-fibers. We attempted to clarify the association between functional dyspepsia (FD) and SCN10A non-synonymous polymorphisms (2884 A>G, 3218 C>T and 3275 T>C)., Methods: The study was performed in 642 subjects (345 with no symptoms and 297 with FD). We employed a multiplex polymerase chain reaction single-strand confirmation polymorphism (PCR-SSCP) method to detect the gene polymorphisms., Results: The 3218 CC homozygotes had a reduced risk for the development of FD [odds ratio (OR) 0.589; 95 % confidence interval (CI) 0.402-0.864; p = 0.0067]. In addition, both 2884 A>G and 3275 T>C, which were in linkage disequilibrium, were also associated with the development of FD (p = 0.039 and 0.028, respectively). Each 2884 G carrier, 3218 CC homozygote, and 3275 C carrier had a reduced risk for the development of both epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). The subjects with the 2884 G allele, 3275 C allele, and no 3218 T allele had a reduced risk for FD (OR 0.618; 95 % CI 0.448-0.853; p = 0.0034). This haplotype was associated with a reduced risk for both EPS and PDS (p = 0.0011 and 0.0056, respectively). In addition, there was a significant association between FD and this haplotype in Helicobacter pylori-negative subjects (OR 0.463; 95 % CI 0279-0.9768; p = 0.0029)., Conclusion: We conclude that genetic polymorphisms of SCN10A are closely associated with FD (both EPS and PDS), especially in H. pylori-negative subjects, in Japanese.

Background/aims: There have been reports showing the protective role of inducible heat-shock protein (HSP) 70 in gastric epithelial cells. An A to G transition at the 1267 position HSP70-2 gene has been shown to be associated with a different level of HSP70 mRNA expression. We aimed to clarify the effect of HSP70-2 polymorphism on the risk of peptic ulcer diseases in a Japanese population., Methodology: A total of 519 subjects participated in this study. All subjects underwent upper gastroscopy. Restriction fragment length polymorphism analysis was performed for polymorphisms at 1267 of HSP70-2 gene in all the subjects., Results: After gastroscopy, 109, 53 and 357 subjects were diagnosed as gastric ulcer, duodenal ulcer and non-ulcer subjects, respectively. Although, there were no significant differences of HSP70-2 genotype distributions among nonulcer subjects, overall ulcer, gastric and duodenal ulcers when the subjects were divided into two groups according to age distribution, logistic regression analysis showed that the BB genotype increased the risk of duodenal ulcer in subjects 60 years and older. (Gender, status of H. pylori infection and NSAID use adjusted OR=3.12, 95%CI=1.33-7.35, p=0.009)., Conclusions: It appears that polymorphism of HSP70-2 gene is not directly associated with the susceptibility to peptic ulcer diseases but BB genotype is associated with an increased risk of duodenal ulcer in older subjects in the Japanese population.

Background: There is evidence that changes in MDR1 function and/or expression contribute to the pathogenesis of inflammatory disorders of the gastrointestinal tract., Aims: We aimed to investigate the effect of C3435T polymorphism of the MDR1 gene on histological chronic gastritis, and on the risk of peptic ulcer diseases., Methods: Restriction fragment length polymorphism analysis was performed for polymorphisms at C3435T in the MDR1 gene in 556 cancer-free subjects including 116 gastric and 60 duodenal ulcers, and 380 non-ulcer subjects. Gastritis scores in the antrum were assessed according to the updated Sydney system in 384 subjects., Results: We did not find a significant association between MDR1 genotype and gastritis scores in any of the 384 subjects. However, the 3435T carrier was significantly associated with a higher degree of neutrophil infiltration in H. pylori-positive subjects (CC vs. T carrier: p=0.0495). When the H. pylori positive subjects were divided according to generation, the 3435T carrier was significantly associated with a higher degree of neutrophil infiltration in subjects more than 65 years of age (CC vs. T carrier: p=0.03). Also, the MDR1 3435 TT genotype was significantly associated with a higher degree of atrophy and intestinal metaplasia in the same generation (atrophy, TT vs. C carrier: p=0.038, intestinal metaplasia, TT vs. C carrier: p=0.016). No association was found between MDR1 genotypes and risk of peptic ulcer diseases., Conclusions: It appears that the C3435T polymorphism of MDR1 influences H. pylori-related inflammatory conditions in the stomach, especially in older subjects.

Background: Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human cancers. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of gastric cancer (GC) and peptic ulcer diseases, and with the severity of Helicobacter pylori-induced gastritis in Japanese population., Methods: The rs11614913 (C>T), rs2910164 (G>C), and rs3746444 (A>G) SNPs were genotyped in 552 GC, and 697 non-cancer subjects, including 141 gastric and 73 duodenal ulcer, and 483 non-ulcer subjects. The degree of histologic gastritis was classified according to the updated Sydney System, and the serum pepsinogen levels were measured in selected 579 and 204 cases., Results: The rs2910164 CC genotype held a significantly higher risk of GC when compared to non-cancer subjects (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.02-1.66, p =.03). Similarly, the rs2910164 C carrier was associated with higher risk of GC when compared to both non-cancer and non-ulcer subjects (OR = 1.39, 95%CI = 1.00-1.93, p =.05, adjusted OR = 1.57, 95%CI = 1.09-2.27, p =.016, respectively). The rs2910164 CC genotype was associated with non-cardia and upper third, diffuse type and advanced stage GC. The rs11614913 TT genotype was associated with higher degree of mononuclear cell infiltration (score 0-1 vs 2∼, adjusted OR = 1.62, 95%CI = 1.05-2.49, p =.03)., Conclusions: The rs2910164 (G>C) SNP in the miR-146a is associated with susceptibility to GC. In addition, the rs11614913 (C>T) SNP in the miR-196a2 is associated with the degree of H. pylori-induced mononuclear cell infiltration., (© 2010 Blackwell Publishing Ltd.)

Objectives: Capsaicin/vanilloid (transient receptor potential vanilloid 1, (TRPV1) receptor has been shown to be expressed in gastrointestinal tract and play a role as a member of sensory ion channel superfamily. The G315C polymorphism affects the TRPV1 gene and alters its protein level. We aimed to investigate the effect of TRPV1 G315C polymorphism on functional dyspepsia (FD) in a Japanese population., Methods: TRPV1 G315C polymorphism was genotyped in 98 subjects with no upper abdominal symptoms and 109 patients with FD. Severity of 7 upper gastrointestinal symptoms was assessed during cold water, and cold carbonated water drinking for randomly selected 20 healthy subjects., Results: We found a significant inverse association between TRPV1 315CC genotype and FD [CC vs. others; odds ratio (OR)=0.40, 95% confidence interval (CI)=0.38-0.82]. We also found that the same genotype held a lower risk of both epigastric pain syndrome (OR=0.25, 95% CI=0.09-0.73), postprandial syndrome (OR=0.27, 95% CI=0.07-0.96) according to Rome III, and Helicobacter pylori positive FD (OR=0.28, 95% CI=0.10-0.79). The evolution of symptom severity scale of 7 total symptoms (P=0.004), and heavy feeling in stomach (P=0.02) during cold carbonated water drinking were significantly lower among 315CC genotypes compared with others., Conclusions: Homozygous TRPV1 315C influences the susceptibility to FD through altering the upper gastrointestinal sensation.

From epidemiological evidence a high salt diet is a risk factor for gastric cancer, independent of Helicobacter pylori infection, and animal studies have shown that salt promotes carcinogenesis. The G-protein β 3(GNB3) C825T polymorphism has been linked with hypertension, salt sensitivity and multiple diseases. Our aim in this study was to clarify any association of the GNB3 C825T polymorphism with gastric cancer risk in Japanese. We examined 161 patients with gastric cancer and 183 control subjects. All underwent stomach biopsy by endoscopic procedures, and extracted DNA was genotyped using a primer pair including the GNB3 C825T polymorphism area by PCR-based restriction fragment length polymorphism (PCR-RFLP). Logistic-regression analysis was performed to assess the impact of the genetic polymorphism. Overall comparison of genotype frequency showed the CT genotype in control patients to be relatively infrequent, but no statistically significant differences were found. However, on comparison of subtypes of gastric cancer (intestinal and diffuse), a significantly increased risk of diffuse type of gastric cancer was foudn for the TT genotype (odds ratio compared to CC, 3.1, 95%CI 1.1-8.6, p=0.03). In conclusion, the TT genotype of GNB3 was associated with diffuse type of gastric cancer. The mechanism of the GNB3 polymorphism interaction with gastric cancer development needs to be clarified by future study.

A complex interaction of host genetic and environmental factors may be relevant in the development of Helicocobacter pylori-related gastric carcinogenesis. We investigated the effect of vascular endothelial growth factor (VEGF) gene polymorphisms on the risk of gastric cancer (GC) and peptic ulcer diseases in a Japanese population. The G1612A(rs10434) and C936T(rs3025039) polymorphisms in the 3' untranslated region (3'-UTR) of VEGF gene were genotyped in a total of 844 subjects including 385 GC, 143 ulcer including 98 gastric ulcer (GU), 45 duodenal ulcer (DU), and 316 nonulcer subjects. The 1612A carrier held a significantly higher risk of GC when compared to both noncancer and nonulcer (overall noncancer vs. GC; OR = 1.61, 95% CI = 1.17-2.21, P = 0.0038, nonulcer vs. GC; OR = 1.54, 95% CI = 1.07-2.22, P = 0.0197). The 1612A carrier was more closely associated with an increased risk of noncardiac cancer (OR = 1.64, 95% CI = 0.17-2.21, P = 0.0038), lower third cancer (OR = 1.97, 95% CI = 1.30-3.00, P = 0.002), and Lauren's diffuse-type cancer (OR = 1.75, 95% CI = 1.24-2.46, P = 0.001), while the same genotype was not associated with the progression of GC. The C936T genotype was not associated with a risk of GC and its progression. Both the G1612A and C936T genotypes were not associated with the risk of peptic ulcer diseases. Our data suggest that the G1612A, but not C936T polymorphisms in the 3'-UTR of VEGF gene is associated with the susceptibility to GC in the Japanese population.

Background: A complex interaction of genetic and environmental factors is relevant in gastric carcinogenesis. Previous studies reported that the expression of RANTES is enhanced in Helicobacter pylori-infected gastric mucosa. Elevated serum level of RANTES in gastric cancer patients was also reported. We aimed to clarify the effect of RANTES promoter polymorphism on the risk of gastric cancer (GC) in a Japanese population., Materials and Methods: A total of 191 GC and 335 non-cancer patients including H. pylori-positive gastritis (n=180) and H. pylori- negative healthy stomach (n=155) were genotyped for polymorphisms at -28 C/G in the RANTES gene promoter region., Results: RANTES promoter genotype distributions were not significantly different among GC, overall non-cancer patients, healthy stomach and gastritis. In the comparison of genotype frequency between GC and healthy stomach, only a weak correlation was found between -28G/G genotype and GC in individuals more than 70 years of age (odds ratio (OR)=7.65, 95% confidence interval (CI)=0.78-75.0, p=0.07), with advanced stage (OR=6.58, 95% CI=0.72-59.77, p=0.07), lymph node metastasis (OR=7.20, 95% CI=0.79-65.46, p=0.06) and peritoneal dissemination (OR=10.93, 95% CI=0.96-124.64, p=0.07)., Conclusion: The effect of -28 C/G polymorphism in the RANTES gene promoter on GC development may not to be very strong. The role of RANTES promoter polymorphism in gastric carcinogenesis needs further evaluation.

Background/aims: The role of genetics in the susceptibility to functional dyspepsia (FD) is not well established. Cholecystokinin (CCK) is released from enteroendocrine cells in the duodenal mucosa after food ingestion and signals satiation through peripheral or central actions. A common polymorphisms of CCK and it's receptor gene has been shown to be associated with panic disorder and schizophrenia. It was investigated the prevalence of CCK polymorphism in dyspeptic patients in a Japanese population., Methodology: A total of 124 dyspeptic patients, 119 non-symptomatic healthy controls participated in this study. Dyspeptic patients were also classified by Rome III criteria. T779C of Cholecystokinin (CCK)-1 intron 1, by polymerase chain reaction-restriction fragment length polymorphism. H. pylori infection status was examined by histology or antibody against H. pylori., Results: Although frequency of CCK-1 polymorphisms in overall dyspeptic patients, subgroups by Roma III criteria and non-symptomatic healthy controls did not show any significant differences, 779 T carriers significantly increased the risk of postprandial syndrome (PDS) in male subjects (53.5% vs, 84.2; OR = 4.63, 95% CI = 1.24-17.31, p = 0.018). This significant association was also remained after logistic regression analysis with adjustment for age and H. pylori infection status (OR = 4.99, 95% CI = 1.31-18.95, p = 0.018). In female and different H. pylori infection status, no significant association was observed between CCK-1 polymorphisms and dyspepsia., Conclusion: Our data suggest that the 779 T carriers of CCK-1 intron 1 is associated with an increased risk of PDS in Japanese male subjects.

Objective: Mannan-binding lectin (MBL) is an important constituent of the innate immune system, and deficiency of MBL has been reported to increase the overall susceptibility of an individual to infectious disease. Codon 54 G/A variant of exon 1 (B allele) affects MBL2 gene and alters its activity. We investigated the influence of MBL2 variant on the risk of gastroduodenal diseases and on the severity of Helicobacter pylori-induced gastritis in a Japanese population., Methods: One hundred and two gastric ulcers, 48 duodenal ulcers, 275 nonulcer participants were included in this study. B allele of the MBL2 gene was detected by polymerase chain reaction based restriction fragment length polymorphism. The severity of the histological chronic gastritis in antral biopsy specimens were classified according to the updated Sydney system., Results: MBL2 B allele was significantly associated with severity of gastric mucosal atrophy and intestinal metaplasia (atrophy, G/G vs. G/A vs. A/A; P=0.02, A/A vs. others; P=0.009, intestinal metaplasia; G/G vs. G/A vs. A/A; P=0.03, A/A vs. others; P=0.004). When participants were divided into the following three groups according to the severity of gastric atrophy: the nonatrophic gastritis (NA) group, the severe atrophic gastritis (SA) group, and mild atrophic gastritis (MA) group, the frequency of A/A was significantly higher in the SA group than in others (SA vs. MA; odds ratio=8.42, 95% confidence interval=1.05-67.45, SA vs. others; odds ratio=10.06, 95% confidence interval=1.26-80.45)., Conclusion: Our data suggest that the MBL2 codon 54 B allele is associated with a risk of developing more severe gastric mucosal atrophy in H. pylori-infected Japanese patients.

Background/aims: A complex interaction of genetic and environmental factors is relevant in gastric carcinogenesis. Cyclin D1 (CCND1) is known to regulate function in G1 arrest and therefore, may play an important role in carcinogenesis. The present study aimed to clarify the effect of G870A polymorphism of the CCND1 gene on the risk of gastric cancer (GC) in a Japanese population., Methodology: Restriction fragment length polymorphism analysis was performed for polymorphisms at 870GA in the CCND1 gene in 392 GC and 359 cancer-free subjects including 203 H. pylori positive gastritis and 156 H. pylori negative healthy stomach, Results: Non significant association was found between CCND1 G870A genotypes and risk of GC when compared to that of all non-cancer subjects (AA vs. GG+GA: OR = 1.13, 95% CI = 0.81-1.58, A carrier vs. GG: OR = 1.13, 95% CI = 0.81-1.56), healthy stomach(AA vs. GG+GA: OR = 1.27, 95% CI = 0.81-2.00, A carrier vs. GG: OR = 1.13, 95% CI = 0.8-1.84) and gastritis. (AA vs. GG+GA: OR = 1.03, 95% CI = 0.7-1.53, p = 0.92, A carrier vs. GG: 1.06, 95% CI = 0.72-1.56, p = 0.77) No association was found between CCND1 genotypes and any of clinico-pathological features of GC., Conclusion: It appears that the G870 polymorphism of CCND1 is not associated with the risk of GC in the Japanese population.

Background/aims: A complex interaction of host genetic and environmental factors may be relevant in the development of Helocobacter pylori (H. pylori) related gastroduodenal diseases. Catechol-O-methyltransferase (COMT) is expressed catalyzes the methylation of various endobiotic and xenobiotic substances and thus might protect DNA from oxidative damage. We aimed to clarify the effect of COMT functional polymorphism on the severity of histological gastritis in a Japanese population., Methodology: 203 subjects were included in this study. Restriction fragment length polymorphism analysis was performed for polymorphisms at codon 158 in the COMT gene. Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system., Results: COMT genotype distribution in the study subjects was 158Val/Val (51.2%), 84Val/Met (41.4%), and 15Met/Met (7.4%). It was within the Hardy-Weinberg equilibrium (p = 0.73). In over all subjects, the degree of intestinal metaplasia tended to be lower among 158Met/Met when compared to Val/Val (Val/Val vs. Met/Met; 0.59 +/- 0.93 vs. 0.13 +/- 0.52, p = 0.052). Among H. pylori infected subjects, the degree of intestinal metaplasia was significantly lower among 158Met carriers in 50 years or older age (Val/Val vs. Met carriers; 1.20 +/- 1.06 vs. 0.75 +/- 1.08, p = 0.0436). No significant association was found between COMT genotypes and the degree of gastritis in different gender, Conclusion: Our data suggest that COMT gene 158Met polymorphism is associate with a reduced risk of developing more severe intestinal metaplasia in H. pylori infected older subjects.

Background: Inflammation is a key factor in the process of carcinogenesis from chronic gastritis induced by Helicobacter pylori. Selenoprotein S (SEPS1) is involved in the control of the inflammatory response in the endoplasmic reticulum (ER). Recently the -105G>A polymorphism in the promoter of SEPS1 was shown to increase pro-inflammatory cytokine expression. We examined the association between this polymorphism and the risk of gastric cancer., Methods: We took stomach biopsies during endoscopies of 268 Japanese gastric cancer patients (193 males and 75 females, average age 65.3), and 306 control patients (184 males and 122 females, average age 62.7) and extracted the DNA from the biopsy specimens. All subjects provided written informed consent. For the genotyping of the SEPS1 promoter polymorphism at position -105G>A, PCR-RFLP methods were used and the PCR products were digested with PspGI. Logistic-regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, sex, and H. pylori infection status., Results: Among cases, the distribution of genotypes was as follows: 88.4% were GG, 11.2% were GA, and 0.4% were AA. Among controls, the distribution was as follows: 92.5% were GG, 7.2% were GA, and 0.3% were AA. Among males, carrying the A allele was associated with an increased odds of gastric cancer, compared with the GG genotype (OR: 2.0, 95% CI 1.0-4.1, p = 0.07). Compared with the GG genotype, carrying the A allele was significantly associated with increased risks of intestinal type gastric cancer (OR: 2.0, 95%CI 1.0-3.9, p < 0.05) as well as of gastric cancer located in the middle third of the stomach (OR: 2.0, 95%CI 1.0-3.9, p < 0.05)., Conclusion: The -105G>A promoter polymorphism of SEPS1 was associated with the intestinal type of gastric cancer. This polymorphism may influence the inflammatory conditions of gastric mucosa. Larger population-based studies are needed for clarifying the relation between inflammatory responses and SEPS1 polymorphism.

Background: Prostaglandins (PGs), catalyzed from arachidonic acid by cyclooxygenase (COX), are involved in a variety of physiological processes in the stomach. COX-1 has been regarded as a constitutively expressed enzyme that generates prostaglandins for gastrointestinal integrity. We investigated the association between the potentially functional polymorphism T-1676C in the COX-1 gene promoter and functional dyspepsia (FD) in the Japanese population., Methods: The study was performed in 272 subjects (185 with no upper abdominal symptoms and 87 with FD). We employed the PCR-SSCP method to detect the gene polymorphism., Results: Overall, female sex had a 2-2.5-fold risk for the development of FD compared with male sex, whereas the COX-1 gene polymorphism and Helicobacter pylori infection were not associated with susceptibility to FD. However, in female subjects, -1676T allele carriers had a significantly increased risk for the development of FD (OR 2.70, 95%CI 1.04-6.99, p = 0.041), especially the epigastric pain syndrome (EPS) subgroup (OR 4.07, 95%CI 1.15-14.4, p = 0.029)., Conclusions: Our results provide the first evidence that the COX-1 gene polymorphism is significantly associated with the development of the EPS subgroup of FD in female subjects.

Background/aims: The role of genetics in the susceptibility to functional dyspepsia (FD) is unclear. Catechol-O-methyltransferase (COMT) has been an important enzyme in brain gut axis and pain sensitivity. Polymorphism in codon 158 of the COMT gene influences its activity. This study aimed to clarify the association between COMT polymorphism and dyspepsia in a Japanese population., Methodology: 91 dyspeptics and 94 non-dyspeptic subjects enrolled in this study. Dyspeptic symptoms were divided into 9 categories. COMT gene val158met polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism., Results: The frequency of Met carriers was lower in over all dyspeptics than healthy control but the difference was not significant (OR=0.79, 95%CI=0.44-1.41) However, when the interaction between age, gender, H. pylori infection status and the number of COMT 158Met alleles was assessed using ANOVA, a slight interaction with gender + age + COMT polymorphism was found in relation to overall dyspeptics (p=0.0476) No correlation was found between COMT polymorphism and any of 9 symptoms., Conclusions: The data suggest that the COMT genotype seems to influence the susceptibility of dyspepsia when it interacts with gender and age. The role of genetics in the development of dyspepsia needs to further evaluation.

Background/aims: Non-steroidal anti-inflammatory drugs (NSAIDs) aggravate or ameliorate clinical disease activity in patients with ulcerative colitis (UC). UC is associated with increased local production of prostanoids. This study attempted to clarify the relationship between cyclooxygenase-1 (COX1) gene polymorphisms (T-1676C and A-842G/C50T) and ulcerative colitis in a Japanese population., Methodology: The study was performed on 108 patients with UC (mean age: 39.1 years, M:F=56:52) and 293 healthy controls (mean age: 49.0 years, M:F=161:132). The PCR-SSCP method was employed to detect COX1 polymorphisms using DNA extracted from peripheral blood cells., Results: No A-842G/C50T polymorphism was detected in all 401 Japanese subjects. The frequency of -1676C allele of COX1 gene in HC group and UC group was 48.8% and 48.1%, respectively. T-1676C genotypes of COX1 did not show significant association with UC risk. In addition, these genotypes were not also associated with the clinicopathological parameters of UC., Conclusions: This research suggests that COX1 promoter polymorphisms (T-1676C and A-842G/ C50T) may not be associated with the risk of developing ulcerative colitis in a Japanese population.

Background/aims: Transcription factor Nrf2 regulates the expression of detoxifying and antioxidant genes. Three promoter polymorphisms of this gene have been identified. This study attempted to clarify the relationship between Nrf2 gene polymorphism and ulcerative colitis in a Japanese population., Methodology: The study was performed in 89 patients with ulcerative colitis (mean age: 40.2 years, M:F = 47:42) and 141 healthy volunteers (mean age: 38.7 years, M:F = 75:66). The PCR-SSCP method was employed to detect Nrf2 polymorphisms using DNA extracted from peripheral blood cells., Results: Comparison of genotype frequency, -686*-684 A* G/A*G genotype was significantly lower in the UC group than those in the HC group (OR = 0.45, 95% CI:0.22-0.93, p = 0.029) and G*G carrier was higher in the UC group, especially in female subjects. Furthermore, -686*-684 G*G carrier was more closely associated with chronic continuous phenotype (OR = 2.57, 95% CI:1.01-6.60, p = 0.043). On the other hand, no association between -650 genotype and ulcerative colitis was found., Conclusions: The -686*-684 genotype of Nrf2 gene may be associated with the development of ulcerative colitis.

Background: The relationship between endoscopic appearances such as endoscopic gastritis and duodenitis and dyspeptic symptoms has not been clearly demonstrated. We aimed to clarify the association of endoscopic appearances with Helicobacter pylori infection, histological severity of gastritis, and dyspeptic symptoms in a Japanese population., Methods: We enrolled 87 dyspeptic and 93 nondyspeptic subjects in this study. All subjects underwent gastroscopy, and patients with active peptic ulcer disease, reflex esophagitis with erosion, polyps >1 cm, or cancer were excluded. Endoscopic appearances in patients with dyspeptic symptoms and in those without were assessed retrospectively on the basis of endoscopic images. The degree of atrophy by the Kimura-Takemoto classification system was also assessed. Helicobacter pylori infection status was examined by histology or antibody against H. pylori. Histological severity of inflammation and glandular atrophy in the antrum were assessed according to the updated Sydney System. The odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression using the variables age, sex, H. pylori infection status, and all endoscopic appearances., Results: The degree of atrophy tended to be lower among dyspeptic patients (P = 0.06). Among all endoscopic appearances, the liner redness (friability) in the antrum (OR = 3.90, 95% CI = 1.20-12.64) and duodenal ulcer (DU) scarring (OR = 3.41, 95% CI = 1.08-10.79) were independently associated with dyspepsia. Histological severity of inflammation and glandular atrophy were not associated with dyspeptic symptoms. Also, no correlation was found between endoscopic appearances and any of the different subgroups of dyspeptic symptoms. Patients with friability in the antrum and DU scar, which correlated with dyspeptic symptom showed some of communal symptoms such as epigastric pain, epigastric discomfort, hypochondriac pain, early satiation/postprandial fullness, and belching, but they differed considerably with respect to H. pylori positivity and the histological severity of gastritis., Conclusions: Some endoscopic appearances such as friability in the antrum and DU scarring may be associated with dyspeptic symptoms, and endoscopic appearances may be useful markers to perform clinical implementation reflecting an individual's pathophysiology of dyspeptic symptoms.

Background: Cyclin D1 (CCND1) is known to regulate function in G1 arrest and therefore may play an important role in carcinogenesis. The aim of this study was to investigate the effect of G870A polymorphism of the CCND1 gene on gastric precancerous condition, on histological chronic gastritis, and on the risk of peptic ulcer diseases., Methods: Restriction fragment length polymorphism analysis was performed for polymorphisms at 870GA in the CCND1 gene in 524 cancer-free subjects, including 111 gastric and 54 duodenal ulcers, and 359 non-ulcer subjects. Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system in 384 subjects., Results: CCND1 genotype was significantly associated with the severity of intestinal metaplasia by the Kruskal-Wallis test, and this tendency was especially stronger among older subjects of 61 years or older (overall subjects: p=0.035, 61 years approximately : p=0.007). We also found that the 870AA genotype held a significant high risk of intestinal metaplasia [Helicobacter pylori infection adjusted odds ratio (OR)=1.8, 95% confidence interval (CI)=1.03-3.15, p=0.04]. The same genotype was more closely associated with the risk of intestinal metaplasia in older subjects of 61 years or older (H. pylori infection adjusted OR=3.45, 95% CI=1.48-8.08, p=0.004). A non-significant association was found between CCND1 G870A genotypes and the risk of peptic ulcer diseases as well as histological severity of acute or chronic inflammation., Conclusions: It appears that the G870A polymorphism of CCND1 is associated with gastric premalignant condition especially in older subjects.

Inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia (FD). However, detailed data regarding the relationship between the genetic regulatory factors of inflammation and FD are not available. We investigated the associations between FD and genetic polymorphisms of molecules associated with inflammation or immune response (IL-17A, -17F and MIF). The study was performed with 278 subjects (188 with no upper abdominal symptoms and 90 with FD according to the Roma III criteria). We employed the PCR-SSCP (multiplex PCR for IL-17A and -17F) method to detect the gene polymorphisms. Overall, the polymorphisms of the IL-17A, -17F and MIF genes were not correlated with the susceptibility to FD. However, the MIF -173C allele carrier had a significantly increased risk for the development of epigastric pain syndrome (EPS) of FD (OR, 2.12; 95% CI, 1.00-4.49; p=0.0497). In Helicobacter pylori (H. pylori)-infected cases, the number of IL-17F 7488T alleles was positively correlated with the development of EPS (OR, 11.3; 95% CI, 1.23-103.2; p=0.032), while the IL-17F T/T homozygote and the MIF -173C carrier had an increased risk for EPS (OR, 10.4; 95% CI, 1.17-92.3; p=0.036 and OR, 3.66; 95% CI, 1.19-11.3; p=0.024, respectively). In addition, a significant interaction between the IL-17F 7488 polymorphism and H. pylori infection was shown to increase the activity and inflammation scores (p=0.043 and 0.042, respectively). There were no significant associations between the IL-17A polymorphism and FD. Our results provide the first evidence that the IL-17F and MIF gene polymorphisms are significantly associated with the development of FD, particularly EPS, a subgroup of FD, in H. pylori-infected subjects. The genetic polymorphisms of inflammation or immune response-related molecules are involved in the development of one of the FD subgroups via H. pylori-induced gastric inflammation.

Toll like receptors (TLR) play important roles in the signaling of many pathogen-related molecules and endogenous proteins associated with immune activation. The -196 to -174del polymorphism affects the TLR2 gene and alters its promoter activity. We investigated the influence of the TLR2-196 to -174del polymorphism on the occurrence of non-cardiac gastric cancer (NCGC) in a Japanese population. The study was carried out with 289 patients with NCGC, 309 non-cancer patients with abdominal discomfort and 146 healthy controls. The -196 to -174del TLR2 polymorphism was investigated using the allele-specific polymerase chain reaction method in all of the subjects. The -196 to -174del/del genotype of TLR2 showed a significantly higher frequency in NCGC patients than in healthy controls (adjusted odds ratio [OR] = 6.06; 95% confidence interval [CI] = 1.86-19.72). Similarly, the frequency of the -196 to -174del/del genotype was significantly higher among NCGC patients than in non-cancer patients (adjusted OR = 2.02; 95% CI = 1.22-3.34). The same genotype was associated with an increased risk of both intestinal (OR = 2.00, 95% CI = 1.12-3.60) and diffuse-type (OR = 2.05; 95% CI = 1.11-3.79) histopathology. There were no significant associations between TLR2 genotypes and tumor stage and anatomical location. Our data suggest that the -196 to -174del/del genotype of TLR2 may increase the risk of gastric cancer in the Japanese population.

Background and Aims: Host genetic factors play a key role in gastric carcinogenesis, but the mechanism has not been clarified. The multi-drug resistance 1 (MDR1) gene mediates the expression of P-glycoprotein, which has a role in active transport of various substrates, including xenobiotics, and thus has a protective function in various tissues and organs like gastrointestinal epithelial cells. C3435T polymorphism in exon 26 of the MDR1 gene influences P-glycoprotein expression and activity in the gastrointestinal tract. We investigated the influences of MDR1 gene polymorphism on the risk of gastric cancer., Method: The study was performed on 157 patients with gastric cancer (GC) and 104 patients without GC as the control group. C3435T polymorphism of MDR1 was investigated by PCR-RFLP in all of the patients., Results: The MDR1 3435 TT genotype showed a significantly higher frequency in controls than in GC patients (OR = 0.43; 95% CI = 0.23-0.79). There were no significant differences of the CT and CC genotype frequencies between GC patients and controls. We also found that the 3435TT genotype of MDR1 was associated with a lower risk of non-cardiac cancer (OR = 0.42; 95% CI = 0.23-0.79), middle-third cancer (OR = 0.36; 95% CI = 0.17-0.77), advanced cancer (OR = 0.31; 95% CI = 0.13-0.73), venous invasion (OR = 0.30; 95% CI = 0.10-0.91), and lymph node metastasis (OR = 0.28; 95% CI = 0.13-0.65)., Conclusion: Our data suggest that 3435T/T polymorphism of MDR1 is associated with a reduced risk of gastric cancer in the Japanese population.

Cyclooxygenase-1 (COX-1) has been regarded as a constitutively expressed enzyme that generates prostaglandins for gastrointestinal integrity. We attempted to clarify the association between potentially functional polymorphisms (T-1676C and A-842G/C50T) in the COX-1 gene promoter and gastroduodenal disorders in a Japanese population. The study was performed with 480 stocked DNAs from subjects (gastric ulcers in 93 subjects and duodenal ulcers in 44) with no evidence of gastric malignancy. We employed the PCR-SSCP method to detect gene polymorphisms. The severity of histological chronic gastritis in antral biopsy specimens was classified according to the updated Sydney system. The T-1676C polymorphism was not associated with either gastric mucosal atrophy or infiltration of inflammatory cells into gastric mucosa. In non-NSAID (non-steroidal anti-inflammatory drug) users, male gender and Helicobacter pylori (HP) infection were significantly associated with both gastric and duodenal ulcers, whereas the -1676T allele carrier was significantly associated with only gastric ulcers (OR, 2.86; 95% CI, 1.29-6.34). In NSAID users, the number of -1676T alleles was significantly associated with developing gastroduodenal ulcers (OR, 5.80; 95% CI, 1.59-21.1), whereas male gender and HP infection were not. The -842T/ C50T polymorphism was not detected in any of the 480 Japanese subjects. In conclusion, a carrier of the -1676T allele in the COX-1 gene promoter, as well as HP infection and male gender, seem to be significant risk factors for developing gastric ulcers, and the number of -1676T alleles was also a significant risk factor for the NSAID-induced ulcer, whereas the frequency of the A-842G polymorphism was thought to be very rare in the Japanese population.