A genome-wide association study in the Japanese population identifies the 12q24 locus for habitual coffee consumption: The J-MICC Study.

Coffee is one of the most widely consumed beverages worldwide, and its role in human health has received much attention. Although genome-wide association studies (GWASs) have investigated genetic variants associated with coffee consumption in European populations, no such study has yet been conducted in an Asian population. Here, we conducted a GWAS to identify common genetic variations that affected coffee consumption in a Japanese population of 11,261 participants recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Coffee consumption was collected using a self-administered questionnaire, and converted from categories to cups/day. In the discovery stage (n = 6,312), we found 2 independent loci (12q24.12-13 and 5q33.3) that met suggestive significance (P < 1 × 10-6). In the replication stage (n = 4,949), the lead variant for the 12q24.12-13 locus (rs2074356) was significantly associated with habitual coffee consumption (P = 2.2 × 10-6), whereas the lead variant for the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery and replication populations, and the combined analysis using all subjects, revealed that rs2074356 achieved genome-wide significance (P = 2.2 × 10-16 for a meta-analysis). These findings indicate that the 12q24.12-13 locus is associated with coffee consumption among a Japanese population.

Higher dietary cholesterol and ω-3 fatty acid intakes are associated with a lower success rate of Helicobacter pylori eradication therapy in Japan.

Background:Helicobacter pylori infection is a known risk factor for duodenal ulcers, gastritis, and gastric cancer. The eradication of H. pylori is successful in treating these disorders; however, the success rate of eradication therapy is declining. There may be an interaction with nutrient intake to account for this decline.Objective: We investigated the influence of food and nutrient intake on H. pylori eradication therapy.Design: In this study, 4014 subjects underwent endoscopy, were tested for serum antibodies to H. pylori (2046 positive; 51.0%), and had their food intake assessed with the use of a food-frequency questionnaire (FFQ). Of the positive subjects, endoscopies showed that 389 (19.0%) had gastritis and/or duodenal ulcers and were also positive for a 13C-urea breath test (UBT). These 389 subjects received 1-wk H. pylori eradication therapy with lansoprazole, amoxicillin, and clarithromycin and a second UBT 8 wk after treatment. Complete demographic characteristics, serum lipid, insulin, glycated hemoglobin, C-reactive protein (CRP), and creatinine concentrations as well as complete FFQs were available for 352 subjects. Multivariate logistic regression analyses were performed to determine factors that were associated with successful H. pylori eradication therapy.Results: The success rate of eradication therapy was 60.4% (235 of 389). Factors associated with the failure of eradication therapy included increased age (P = 0.02), higher CRP concentrations (P < 0.01), higher dietary cholesterol (P < 0.01) or egg intake (P < 0.01), higher ω-3 (n-3) fatty acid (P = 0.02) or fish intake (P = 0.01), and higher vitamin D intake (P = 0.02). Moreover, the higher vitamin D intake was strongly linked to higher fish intake. A limitation of the study is that we did not assess the antibiotic resistance of H. pyloriConclusions: Our results indicate that higher egg and fish intake may be negatively correlated with successful H. pylori eradication therapy in H. pylori-positive subjects with gastritis and/or duodenal ulcers.

Bioelectrical Impedance Analysis (BIA) of the association of the Japanese Kampo concept "Suidoku" (fluid disturbance) and the body composition of women.

BACKGROUND: In Japanese Kampo medical practice, suidoku (fluid disturbance) is one of the most important concepts for selecting the proper medication. Suidoku is an excessive or uneven distribution of fluid that is indicated by splashing sounds and pitting edema. However, few objective reports about suidoku have been published. Bioelectrical impedance analysis (BIA) uses resistance values obtained from weak electrical currents to estimate body composition, including intracellular and extracellular water and muscle and fat mass. In this study, we used BIA to search for objective factors that can discriminate the various types of suidoku. METHODS: Two hundred twenty-nine patients who visited the Kampo Medicine Clinic of Kyushu University Hospital from June 2010 to August 2015 were divided into non-suidoku (n = 180, 80 male and 100 female), splashing sound (n = 32, 8 male and 24 female) and edema groups (n = 17, 5 male and 12 female). Body composition values were taken from the electronic medical records of InBody730 (a vertical, segmental, multi-frequency analyzer by InBody, Tokyo Japan) testing done at the initial visit. Various parameters of the body composition values of female in the non-suidoku and suidoku groups (splashing sound and edema groups) were compared: there were too few male patients to provide significance. RESULTS: The age and body weight were significantly lower in the splashing sound group than in the non-suidoku group (p < 0.05). In contrast, the body weight of the edema group was significantly heavier than that of the non-suidoku group (p < 0.05). In ROC analysis, the percent Body Fat ≤ 27.8 %, Muscle Mass Index of the Trunk ≤ 6.5 kg/m2, VFA (Visceral fat area) ≤ 5.4 and BMI ≤ 19.2 kg/m2 were associated with splashing sound, and Muscle Mass Index of Legs ≥ 4.8 kg/m2 and BMI ≥ 21.4 kg/m2 were associated with edema. CONCLUSION: Our data suggest that the use of this type of BIA to estimate body composition would be a useful tool for the diagnosis of suidoku for women.

The Relation between Hepatotoxicity and the Total Coumarin Intake from Traditional Japanese Medicines Containing Cinnamon Bark.

Cinnamon bark is commonly used in traditional Japanese herbal medicines (Kampo medicines). The coumarin contained in cinnamon is known to be hepatotoxic, and a tolerable daily intake (TDI) of 0.1 mg/kg/day, has been quantified and used in Europe to insure safety. Risk assessments for hepatotoxicity by the cinnamon contained in foods have been reported. However, no such assessment of cinnamon bark has been reported and the coumarin content of Kampo medicines derived from cinnamon bark is not yet known. To assess the risk for hepatotoxicity by Kampo medicines, we evaluated the daily coumarin intake of patients who were prescribed Kampo medicines and investigated the relation between hepatotoxicity and the coumarin intake. The clinical data of 129 outpatients (18 male and 111 female, median age 58 years) who had been prescribed keishibukuryogankayokuinin (TJ-125) between April 2008 and March 2013 was retrospectively investigated. Concurrent Kampo medicines and liver function were also surveyed. In addition to TJ-125, the patients took some of the other 32 Kampo preparations and 22 decoctions that include cinnamon bark. The coumarin content of these Kampo medicines was determined by high performance liquid chromatography (HPLC). TJ-125 had the highest daily content of coumarin (5.63 mg/day), calculated from the daily cinnamon bark dosage reported in the information leaflet inserted in each package of Kampo medicine. The coumarin content in 1g cinnamon bark decoction was 3.0 mg. The daily coumarin intake of the patients was 0.113 (0.049-0.541) mg/kg/day, with 98 patients (76.0%) exceeding the TDI. Twenty-three patients had an abnormal change in liver function test value, but no significant difference was found in the incidence of abnormal change between the group consuming less than the TDI value (6/31, 19.4%) and the group consuming equal to or greater than the TDI value (17/98, 17.3%). In addition, no abnormal change related to cinnamon bark was found for individual patients. This paper was done to assess the risk of hepatotoxicity by the coumarin contained in Kampo medicines and to clarify whether or not the Kampo preparations in general use that contain cinnamon bark may be safely used in clinical practice.

The association between objective tongue color and endoscopic findings: results from the Kyushu and Okinawa population study (KOPS).

BACKGROUND: The relation between tongue color and gastroesophageal disease is unclear. This study was done to investigate the associations between tongue color (TC), endoscopic findings, Helicobacter.pylori infection status, and serological atrophic gastritis (SAG). METHODS: The participants were 896 residents of Ishigaki Island, Okinawa, aged 28-86 years. The tongue was photographed, esophagogastroduodenoscopy was done, and serum antibody to H.pylori was measured. SAG was defined as a serum Pepsinogen (PG)Ilevel ≤70 ng/ml and a PGI/IIratio ≤3.0. TC was measured by the device-independent international commission on Illumination 1976 L*a*b* color space standards at four points: (1) edge, (2) posterior, (3) middle, and (4) apex. We also calculated the ratio of the tongue edge to the three other measured points to examine the association between the coating of the tongue and the endoscopic and laboratory findings. RESULTS: Participants were excluded who had two or more endoscopic findings (n = 315) or who had SAG without seropositivity to H.pylori (n = 33). The remaining 548 participants were divided into three groups: SAG and seropositive to H.pylori (n = 67), seropositive to H.pylori alone (n = 56), and without SAG and seronegative for H.pylori (n = 425). We divided 425 residents into a single endoscopic finding positive group (n = 207) and a negative group, which served as a control (n = 218). The most frequent single endoscopic finding was esophageal hernia (n = 110), followed by erosive esophagitis (n = 35) and erosive gastritis (EG) (n = 45). EH was significantly associated with TC (2b*/1b*) (P < 0.05). EG was significantly associated with TC (3a*, 3b*) (P < 0.05). Seropositivity to H.pylori was significantly associated with TC (3 L*, 3 L*/1 L*) (P < 0.05, <0.01), and seropositivity to both H.pylori and SAG was significantly associated with TC (3 L*/1 L*) (P < 0.05). Multivariate analysis extracted TC (3a*, 3b*) as an independent factor associated with a differential diagnosis of EG (Odds ratio (OR) 2.66 P = 0.008, OR 2.17 P = 0.045). CONCLUSIONS: The tongue body color of the middle area reflects acute change of gastric mucosa, such as erosive gastritis. Tongue diagnosis would be a useful, non-invasive screening tool for EG.

Nocturnal difference in the ultra low frequency band of heart rate variability in patients stratified by Kampo medicine prescription.

BACKGROUND: The Yo/Yin concept is fundamental to making a Kampo (sho) diagnosis and may be deeply related to the autonomic nervous system. There is, however, little objective data to confirm the validity of these concepts. METHODS AND RESULTS: After diagnosis using standardized Kampo techniques, 20 men and 67 women (mean age, 52.4 years) for whom the prescribed Kampo medication was effective were judged to be correctly classified as Yo- (n=49) or Yin-sho (n=38) and enrolled. Autonomic nervous function was assessed at first visit using HRV obtained from 24-h Holter ECG. Nocturnal ultra low frequency-1 (ULF-1, 0.0001-0.0003 Hz) and ULF-2 (0.0003-0.003 Hz) were significantly higher in the Yin-sho than in the Yo-sho group (P=0.030, P=0.016), suggesting a higher variation of autonomic nervous activity according to sleep stage. On multivariate analysis BMI (≥ 23.0 kg/m(2)) and ULF-1 (≥ 1,150 ms(2)) were identified as independent factors associated with a differential diagnosis of Yo- or Yin-sho (odds ratio [OR], 11.63, P=0.002; OR, 0.30, P=0.038, respectively). When the sleep period was divided into 3 phases, the ULF-1 of the Yin-sho group was significantly higher than that of the Yo-sho group in the late phase of sleep (P=0.023). CONCLUSIONS: On heart rate variability analysis there was a sleep stage-related difference in the autonomic nervous activity of patients treated with standard Yo- and Yin-sho Kampo medicines.

Protein-losing enteropathy during highly active antiretroviral therapy in a patient with AIDS-related disseminated Mycobacterial avium complex infection.

Protein-losing enteropathy (PLE) is defined as a condition in which excess protein loss into the gastrointestinal lumen, due to various causes, is severe enough to produce hypoproteinemia and hypoalbuminemia. We report a 28-year-old Japanese woman with PLE. She had been diagnosed with AIDS and disseminated Mycobacterium avium complex (MAC) infection at age 26. Although highly active antiretroviral and antimycobacterial treatments helped her overcome this critical situation, 2 years after initiation of the treatments, she was readmitted to our hospital because of hypoalbuminemia and edema of the lower extremities, and she was diagnosed, by the use of double-balloon enteroscopy, with PLE due to intestinal lymphangiectasia (IL). The etiology was thought to be obstruction of the mesenteric and retroperitoneal lymphatic drainage systems by MAC lymphadenitis. Even with intensive antimycobacterial treatment, octreotide treatment as a long-acting somatostatin analogue, and a low-fat diet enriched with medium-chain triglyceride, IL was not cured during the follow-up period. In patients with AIDS, complete clinical remission of MAC (especially disseminated MAC) infection is very difficult.