- [Show abstract] [Hide abstract] ABSTRACT: Constipation is a symptom-based disorder, and its definition is mainly subjective. Patients are more concerned with ease of passage and consistency rather than frequency of bowel movement. Studies on bowel movement frequency and stool texture in the general population are sparse, especially in young women. In this cross-sectional study, data obtained from self-administered questionnaires, including age, height, body weight, lifestyle, food habits, anxiety, depressive status, frequency of bowel movements, stool texture, and defecation-related symptoms were analyzed in 245 female Japanese university students. An established semiquantitative questionnaire available for clinical investigation (FFQg) was used to obtain a detailed assessment of food intake and physical activity levels. Of the participants, 21.4% had bowel movements ≤3 times per week and 33.3% had hard or lumpy stools ≥25% and loose (mushy) or watery stools <25% of bowel movements. There was a positive association between infrequent bowel movements and hard or lumpy stools. These two situations both caused similar symptoms such as a sensation of incomplete evacuation and straining. There was no association of bowel movement frequency and stool texture with any specific nutrients and foods, dietary intake, mental status, or physical activity. Several lifestyle factors such as regular bowel movements and hesitation with evacuation were associated with bowel movement frequency and stool texture. Several lifestyle factors, but not mental, physical, or dietary intake factors, were associated with bowel movement frequency and stool texture in young Japanese women. © 2016, Nagasaki University School of Medicine. All rights reserved.
- [Show abstract] [Hide abstract] ABSTRACT: We have previously shown that the Association of Official Analytical Chemists (AOAC) method 2001.03 and 2009.01 not able to measure accurately nondigestible oligosaccharide because they are incapable of hydrolyzing digestible oligosaccharide, leading to overestimation of nondigestible oligosaccharide. Subsequently, we have proposed the improved AOAC methods 2001.03 and 2009.01 using porcine small intestinal disaccharidases instead of amyloglucosidase. In the present study, we tried to determine nondigestible oligosaccharide in marketed processed foods using the improved AOAC method 2009.01 (improved method), and the results were compared with those by AOAC method 2009.01. "In improved method, the percentage of the recovery of fructooligosaccharide, galactooligosaccharide, and raffinose to the label of processed food was 103.0%, 89.9%, and 102.1%, respectively. However, the AOAC method 2009.01 overestimated more than 30% of the quantity of nondigestible oligosaccharide in processed foods, since the margin of error was accepted ±20% on the contents of nondigestible oligosaccharides in processed foods for Japanese Nutrition Labeling. The improved method thus provides accurate quantification of nondigestible oligosaccharides in processed food and allows a comprehensive determination of nondigestible oligosaccharides.
- [Show abstract] [Hide abstract] ABSTRACT: The precise roles of visceral (VAT. or subcutaneous adipose tissue (SAT. on hepatic fat accumulation have not been fully elucidated. In this report, we examined the correlation between VAT or SAT volume and severity of hepatic fat accumulation. In the present study, Sprague-Dawley (SD. rats were fed a standard diet containing 10% fat or a high-fat diet containing 45% or 60% fat for 16 weeks. Abdominal VAT and SAT volume, as well as fat percentage of the liver were measured by computed tomography (CT). Hepatic triglyceride (TG. content and histopathological findings of hepatic steatosis were also examined. Abdominal SAT weight/body weight ratio was positively and strongly correlated with abdominal VAT weight/body weight ratio. Fat percentage of the liver by CT evaluation, hepatic TG content, and hepatic steatosis score by histopathological evaluation showed positive correlations with one another. Fat percentage of the liver by CT evaluation and hepatic TG content was positively correlated with both the abdominal VAT weight/body weight ratio and SAT weight/body weight ratio, respectively. Furthermore, hepatic TG content was negatively correlated with the abdominal VAT weight/SAT weight ratio. Our data suggest that abdominal SAT accumulation is positively correlated with hepatic steatosis in SD rats, rather than abdominal VAT accumulation. Further investigations are needed in order to clarify the precise mechanisms of SAT and VAT effects on the development of hepatic fat accumulation.
- [Show abstract] [Hide abstract] ABSTRACT: Depression has been reported to be more prevalent among diabetic patients than non-diabetic individuals. Although depression and diabetes are causally and bi-directionally related, the influence of food intake frequency on depressive symptoms in diabetic patients has not been fully evaluated. This cross-sectional study analyzed data obtained from 89 patients with type 2 diabetes who completed self-administered questionnaires regarding food intake frequency, diabetic variables, physical activity and depressive states. The prevalence of a "definite" depressive state was 16.9%. The duration of diabetes, hemoglobin A1c levels, diabetic microvascular complications and physical activity levels were similar between depressed and non-depressed patients. Daily intakes of total lipids, n-6 polyunsaturated fatty acids and lipid energy ratios were significantly lower, and the carbohydrate energy ratio was significantly higher in depressed than in non-depressed patients. Coffee consumption was inversely associated with depressive symptoms, but no significant association was found between tea or green tea consumption and depressive symptoms. The logistic regression analysis showed that coffee consumption was an independent predictor of non-depressed status in diabetic patients. This might be due to biologically active compounds containing in coffee other than caffeine.
- [Show abstract] [Hide abstract] ABSTRACT: AimThe development of fibrosis is considered an important phase in the progress of non-alcoholic steatohepatitis (NASH) towards the end stage of liver disease, including cirrhosis. However, few small animal models can display NASH-associated fibrosis. We aimed to establish a dietary model of NASH with rapid progression to fibrosis using genetically normal rats.Methods Nine-week-old male Sprague-Dawley rats were fed with normal, high-fat (HF), or two types of high-fat and high-cholesterol (HFC) diets for 9 weeks (n = 5 each). All HFC diets contained 1.25% or 2.5% cholesterol.ResultsThe rats fed with the HF diet developed mild steatosis and inflammation without fibrosis at 18 weeks of age, whereas all rats given the HFC diet developed obvious steatosis and inflammation with hepatocyte ballooning and fibrosis. Two of five (40%) rats given the HFC diet containing 2.5% cholesterol progressed to liver cirrhosis. Hepatic total cholesterol levels were significantly higher in rats given the HFC, than the normal or HF diets. The HFC diet significantly and dose-dependently decreased microsomal triglyceride transfer protein expression. Cholesterol tended to suppress carnitine palmitoyltransferase activity and ATP-binding cassette transporter G5 expression. Adding cholesterol to the HF diet modified hepatic lipid metabolism at the molecular level.Conclusion The HFC diet induced hepatic features of NASH and eventually progressed cirrhosis in SD rats within 9 weeks.
Dataset: Supplementary material 1
- [Show abstract] [Hide abstract] ABSTRACT: Objective: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. The pathogenesis of IBS is multifactorial. The aim of this study was to investigate the prevalence of IBS using the Rome III criteria in young Japanese women and to assess the effects of mental, physical, dietary and nutritional factors on IBS. Methods: In this cross-sectional study, data obtained from self-administered questionnaires, including age, height, weight, lifestyle, food habits, anxiety and depressive states and IBS-related symptoms, were analyzed in 245 participants. An established semiquantitative questionnaire available for clinical investigation (FFQg) was used to obtain a detailed assessment of food intake and the physical activity levels. Results: The prevalence of IBS was 12.0%. Of the IBS participants, constipation-predominant IBS (25.0%) was more prevalent than the diarrhea-predominant subtype (17.9%). The IBS participants had lower body mass indices, consumed less eggs and milk and were more physically active than the non-IBS participants. In addition, an anxiety state was more common in the IBS participants. Those who hesitated with evacuation of stool and who thought that there is an association between abdominal symptoms, such as constipation and diarrhea, and menstruation were more predominant among the IBS participants. The percentage of individuals who reported often rushing to the toilet within the past year and experiencing borborygmus (rumbling stomach) was greater among the IBS participants. A logistic regression analysis revealed that milk intake was an independent predictor of IBS. Conclusion: The prevalence of IBS observed in this study was similar to that reported in previous studies conducted in Japan and other countries. Mental, physical, dietary and nutritional factors have an impact on IBS.
- [Show abstract] [Hide abstract] ABSTRACT: Endothelial dysfunction is associated with hypertension, atherosclerosis, and metabolic syndrome. Phycocyanin is a pigment found in the blue-green algae, Spirulina, which possesses antihypertensive effect. In this study, we hypothesized that phycocyanin derived from Spirulina exerts antihypertensive actions by improving endothelial dysfunction in metabolic syndrome. Spontaneously hypertensive/NIH-corpulent (SHR/NDmcr-cp) rats were divided into 4 groups then fed a normal diet with or without phycocyanin (2500-, 5000-, or 10 000-mg/kg diet) for 25 weeks. At 34 weeks of age, although systolic blood pressure was not significantly different among groups, phycocyanin-fed groups exhibited a dose-dependent decrease in blood pressure. Serum levels of adiponectin and messenger RNA levels of adiponectin and CCAAT/enhancer-binding protein α in the adipose tissue of rats fed diets containing phycocyanin tended to be higher than those of rats fed a normal diet, but the differences were not statistically significant. Immunohistochemistry analysis showed a significant and positive correlation between aortic endothelial nitric oxide synthase (eNOS) expression levels, a downstream target of the adiponectin receptor, and serum adiponectin levels, although there were no significant differences in eNOS expression among groups. There was also no significant correlation between eNOS expression levels and systolic blood pressure. These results suggest that long-term administration of phycocyanin may ameliorate systemic blood pressure by enhancing eNOS expression in aorta that is stimulated by adiponectin. Phycocyanin may be beneficial for preventing endothelial dysfunction-related diseases in metabolic syndrome.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Patients with primary biliary cirrhosis (PBC) exhibit a variety of clinical manifestations and patterns of disease progression. The aim of this study was to identify genetic determinants of PBC progression. Methods: A total of 52 tag single nucleotide polymorphisms (SNPs) of 11 candidate genes involved in regulating bile acid synthesis were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, -high resolution melting curve analysis, or -direct DNA sequencing in 315 Japanese patients with PBC. Results: In this study, four tag SNPs of CYP7A1 (rs1457043, rs8192870, rs3808607, and rs3824260), two tag SNPs of HNF4A (rs6017340 and 6031587), and one SNP of PPARGC1A (rs8192678) showed a significant association with PBC progression. In addition, a dual luciferase assay revealed that the polymorphism of rs3808607 in CYP7A1 altered the expression of CYP7A1 in HepG2. Specifically, the CYP7A1 promoter carrying the risk G allele for PBC progression induced higher expression of CYP7A1 under both the normal and cholestatic conditions in vitro as compared to another promoter carrying the non-risk T allele. Conclusion: These results suggested that the genetic variants of CYP7A1 and its transcriptional activators (HNF4A and PPARGC1A) may activate bile acid synthesis, resulting in the accumulation of bile acids in hepatocytes and eventually leading to the predisposition to PBC progression. Thus, the regulation of CYP7A1 expression may represent an attractive therapeutic target for cholestatic liver diseases including PBC.
- [Show abstract] [Hide abstract] ABSTRACT: Malnutrition commonly occurs in patients with cancer. This situation can be associated with increased morbidity and mortality. The etiology is not clearly understood but decreased energy intake and increased energy expenditure may be involved. We aimed to investigate the energy metabolic status including energy expenditure in patients with various cancers. The clinical features and energy metabolic status measured by indirect calorimetry of 74 patients with cancer (50 men and 24 women; mean age, 64.7 years) were obtained from the medical records. Hypermetabolism was more common and REE/kg (resting energy expenditure / kg body weight) seems to be more reliable in estimating the true energy expenditure than %REE (measured REE / predicted REE). The REE/kg and VO2/kg (oxygen consumption per minute / kg body weight) varied among cancer types, i.e., they were significantly higher in gastric cancer than in hepatocellular carcinoma. Moreover, REE/kg and VO2/kg was significantly higher in cancer stage IV than in stage I, or stages I and II. Patients with or at risk for malnutrition should receive appropriate nutritional support, which has to be personalized according to tumor site, tumor stage, and the nutritional status of the patient. This nutritional support should improve not only the patients' quality of life but also their survival.
- [Show abstract] [Hide abstract] ABSTRACT: Protein-energy malnutrition (PEM) is frequently seen in patients with liver cirrhosis. This condition is associated with a poor prognosis and reduced survival. We investigated the protein and energy metabolic status, including serum albumin concentration, and resting energy expenditure (REE) and respiratory quotient (RQ) measured by indirect calorimetry in 23 patients with liver cirrhosis (8 men and 15 women; mean age, 60.3 years). The median value of %REE (measured REE/predicted REE) was highest in Child-Pugh grade A and lowest in grade C, and the range of RQ tended to be highest in Child-Pugh grade A and lowest in grade C, although there were not statistically significant (p=0.871 and 0.664, respectively). Serum triglyceride concentration was significantly lower in patients who had an RQ less than 0.85 than in patients who had an RQ of 0.85 or more, and free fatty acid tended to be higher in patients who had an RQ less than 0.85 than in patients who had an RQ of 0.85 or more. Of the 23 patients, 78.3% were in a state of protein and/or energy malnutrition and 47.8% had PEM. Our results suggest that %REE and RQ were not significantly associated with liver function, but the oxidation rate of fat was increased in advanced liver cirrhosis. A longitudinal study in a large population is needed to determine the efficacy of %REE and RQ measurements for adequate nutritional treatment and improvement of patient outcome.
- [Show abstract] [Hide abstract] ABSTRACT: Serum alanine aminotransferase (ALT) concentration is the most commonly used marker for hepatocellular injury. We investigated the suitable cutoff value of serum ALT for the diagnosis or prediction of fatty liver. In 1578 Japanese adults (1208 men, 370 women; 35-69 years of age) who visited our center both in 2000 and between April 2007 and March 2008 (2007-2008), serum ALT concentration was an independent predictor of fatty liver in men in 2000 and in both sexes in 2007-2008. A significant increase in the frequency of fatty liver was detected in participants with elevated serum ALT concentrations, and serum levels of ALT in 2000 were associated with fatty liver in 2007-2008 when the cutoff value was set at 30 IU/L in men and 19 IU/L in women. The frequency of fatty liver in 2007-2008 was significantly lower in participants without fatty liver in 2000 whose serum ALT decreased between 2000 and 2007-2008. Our results suggest that serum ALT might be not only an indicator of fatty liver but also a predictor of the regression of fatty liver, and cutoff values of serum ALT of 30 IU/L in men and 19 IU/L in women are suitable for the screening of fatty liver.
- [Show abstract] [Hide abstract] ABSTRACT: The objective of this study was to test the hypothesis that repeated ingestion of diet containing the leaf extract from a Morus alba (LEM) maintains the postprandial hypoglycemic response and suppresses the progression of insulin resistance in high-sucrose diet-fed KK-Ay mice with spontaneous type 2 diabetes mellitus (DM). This hypothesis is based on our previous studies where LEM competitively inhibited intestinal disaccharidases and suppressed the elevation of postprandial plasma glucose and insulin levels. Ten KK-Ay mice in each group were raised on 0%, 3%, or 6% LEM powder-containing high-sucrose diets for 8 weeks. Blood samples were collected to measure fasting plasma glucose and insulin levels at weeks 2, 4, and 7 after the start of feeding. Urinary glucose excretion was monitored as a parameter of insulin resistance in 3-day intervals. Fasting plasma glucose level and urinary glucose excretion were significantly lower in both 3% and 6% LEM groups compared with the control group throughout the experiment. The plasma insulin of the 6% LEM group was significantly lower compared with the 3% LEM and control groups. Maintenance of low blood glucose and insulin delayed the onset time of urinary glucose excretion and were reflected by the ratio of additional LEM to sucrose in the diet. We observed the suppressive effects on the progression of hyperglycemia and hyperinsulinemia in the repeated ingestion of the LEM-containing diet. Namely, repeated ingestion of the LEM-containing diet reduces insulin resistance and may delay the appearance of DM, especially type 2 DM. Therefore, daily intake of LEM may be suitable for the prevention of obesity and DM.
- [Show abstract] [Hide abstract] ABSTRACT: Accumulating evidence indicates that multiple genetic factors are involved in the pathogenesis of primary biliary cirrhosis (PBC). The aim of this study was to investigate whether polymorphisms of the integrin αV subunit gene (ITGAV), a component of integrin αVβ6, which plays an important role in the process of fibrosis, are associated with susceptibility to the onset and/or progression of PBC. In the primary study, eight tag single nucleotide polymorphisms (SNPs) in ITGAV were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, direct DNA sequencing, or high-resolution melting curve analysis in 309 Japanese patients with PBC who were registered in the National Hospital Organization Study Group for Liver Disease in Japan (PBC cohort I) and 293 gender-matched healthy Japanese volunteers (control subjects). For the replication study, 35 PBC patients who progressed to end-stage hepatic failure and underwent liver transplantation (PBC cohort II) were also analyzed. Three tag SNPs (rs3911238, rs10174098, and rs1448427) in ITGAV were significantly associated with the severe progression of PBC, but not with susceptibility to the onset of PBC, in the primary study (PBC cohort I). Among these SNPs, rs1448427 was also significantly associated with the severe progression to end-stage hepatic failure in the replication study of PBC patients who underwent liver transplantation (PBC cohort II). ITGAV is a genetic determinant for the severe progression of PBC in Japanese patients. Genetic polymorphisms of ITGAV may be useful for identifying high-risk Japanese PBC patients, including those who will require liver transplantation, at the time of initial diagnosis.
- [Show abstract] [Hide abstract] ABSTRACT: Oleuropein, the active constituent of olive leaf extract, possesses anti-oxidant, hypoglycemic, and hypolipidemic activities. We aimed to assess whether the effect of olive leaf extract on hepatic fat accumulation is preventive or therapeutic. Sprague-Dawley (SD) rats were fed a high-fat diet with (ODOD group) or without (HDHD group) olive leaf extract (1,000 mg/kg diet) for 38 weeks. Another group of rats were fed a high-fat diet for 23 weeks, followed by a high-fat diet with olive leaf extract (1,000 mg/kg diet) for 15 weeks (HDOD group). Serology, histopathology, anti-oxidative activity, and liver fatty acid synthesis were compared to those fed a standard diet (LDLD group) at 26 and 41 weeks of age. The serum levels of total cholesterol, triglyceride and aspartate aminotransferase tended to be lower in the ODOD group as compared to the HDHD and HDOD groups, although there were no significant differences. Histopathologically, hepatic steatosis tended to be less evident in the HDOD and ODOD groups as compared to the HDHD group, and lobular inflammation was not observed in the ODOD group at 26 weeks of age. Hepatic thioredoxin-1 staining tended to be less evident in the ODOD group than in the HDHD and HDOD groups at 41 weeks of age. There were no significant differences in hepatic lipogenic enzyme activities between the ODOD group and HDHD/HDOD groups. Our data suggest that olive leaf extract had a preventive, rather than therapeutic, effect on hepatic steatohepatitis in SD rats fed a high-fat diet
- [Show abstract] [Hide abstract] ABSTRACT: Oxidative stress may play an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Oleuropein, the active constituent of olive leaf, possesses anti-oxidant, hypoglycaemic, and hypolipidaemic activities. We aimed to investigate the preventive effects of olive leaf extract on hepatic fat accumulation in a rat model of NASH. Spontaneously hypertensive/NIH-corpulent rats were fed a diet of AIN-93G with or without olive leaf extract (500, 1000, 2000 mg/kg diet, and control; 5 rats each) for 23 weeks. Serological and histopathological findings, anti-oxidative activity, and the alteration of fatty acid synthesis in the liver were evaluated. Histopathologically, a diet of AIN-93G containing more than 1000 mg/kg olive leaf extract had a preventive effect for the occurrence of NASH. Thioredoxin-1 expression in the liver was more evident in rats fed this diet, and 4-hydroxynonenal expression in the liver was less evident in these rats. There were no significant differences in the activities of hepatic carnitine palmitoyltransferase, fatty acid synthase, malic enzyme, and phosphatidic acid phosphohydrolase among the groups. Our data suggest that olive leaf extract may help prevent NASH, presumably through its anti-oxidative activity.
- [Show abstract] [Hide abstract] ABSTRACT: Fatty liver is commonly associated with alcohol or metabolic syndrome. We aimed to examine the longitudinal aspects of fatty liver, and clarify the independent predictors for the development or regression of fatty liver. In the present study, the clinical features of 1578 Japanese adults (1208 men and 370 women; 35 to 69 years of age) who visited our center both in 2000 and 2007-2008 were recorded and compared, including liver status diagnosed by ultrasonography. Of the 1578 participants, 217 (13.8%) showed fatty liver development, and 74 (4.7%) showed fatty liver regression. Logistic regression analysis revealed that body mass index and percentage body fat were strongly associated with the development or regression of fatty liver. Metabolic syndrome-related disorders such as serum levels of total cholesterol, triglyceride, uric acid, and fasting blood glucose were also associated with clinical course to some degree. However, the history of alcohol intake, the presence of metabolic syndrome, blood pressure, and habitual physical exercise were not independent predictors for the development or regression of fatty liver. Our present data suggest that control of body weight in men and the percentage body fat in women are particularly important for the prevention or treatment of fatty liver.
- [Show abstract] [Hide abstract] ABSTRACT: A new prognostic staging system, the SLiDe (S, stage; Li, liver damage; De, des-gamma-carboxy prothrombin) score was recently proposed. We examined 207 HCC patients following hepatic resection to determine the usefulness of this staging system for HCC patients after surgery. Disease-free and overall survival rates were calculated according to the Kaplan-Meier method, and differences between groups were tested for significance using the log-rank test. Regarding disease-free survival, there were no significant differences in survival between SLiDe score 0 vs 1, between score 2 vs 3, and between score 4 vs 5. There were significant differences between 0-1 vs 2-3 (p < 0.01) and between 2-3 vs 4-5 (p < 0.01). Regarding overall survival, there were no significant differences in survival between score 0 vs 1, between score 2 vs 3, and between score 4 vs 5. There were significant differences between 0-1 vs 2-3 (p < 0.05) and between 2-3 vs 4-5 (p < 0.01). The SLiDe score, a staging system that combines tumor factors, a tumor marker and hepatic function, might be a better predictor of prognosis in HCC patients who have undergone hepatic resection.
- [Show abstract] [Hide abstract] ABSTRACT: Gamma-tocopherol is largely metabolized to 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (γ-CEHC), which has natriuretic activity that is mediated via inhibition of 70 pS ATP-sensitive K+ channels in the thick ascending limb of the loop of Henle. However, the effects of γ-tocopherol administration on edema are unclear. To determine the effects of γ-tocopherol administration on pretibial edema, we measured urinary γ-CEHC concentration by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) after administration of γ-tocopherol. Twenty young women who had a history of pretibial edema due to premenstrual syndrome were randomly divided into two groups. The γ-tocopherol group received 4 "γ-tocopherol capsules" (each containing 100mg of γ-tocopherol), and the control group received 4 "placebo capsules" (each containing 250mg of soybean oil) per day for 7 days. Urinary sodium and potassium secretion and urine volume did not increase after cessation of γ-tocopherol administration, yet the degree of pretibial edema improved in all participants in the γ-tocopherol group. The serum γ-tocopherol concentration significantly increased in the γ-tocopherol group. Urinary excretion of γ-CEHC significantly increased after γ-tocopherol administration. Our results suggest that orally administered γ-tocopherol on renal sodium handling is not apparent, but γ-tocopherol is a precursor of prolonged natriuresis of γ-CEHC and may be effective for edema
- [Show abstract] [Hide abstract] ABSTRACT: Unlabelled: Primary biliary cirrhosis (PBC) is a multifactorial disease in which genetic factors rather than environmental factors may predominantly contribute to the pathogenesis. In order to identify the genetic determinants of the disease severity and progression of PBC, we examined an association of seven tag single-nucleotide polymorphisms (SNPs) in the multidrug resistance protein 3 (MDR3/ABCB4) gene in 148 Japanese PBC patients and 150 age- and sex-matched healthy control subjects. SNPs were detected via polymerase chain reaction (PCR) restriction fragment length polymorphism and PCR direct DNA sequencing methods. Subsequently, haplotypes were constructed from three tag SNPs (rs31658, rs31672, and rs1149222) that were significantly associated with progression of PBC. Logistic regression analyses revealed that a Hap 2 haplotype and its homozygous diplotype, Hap 2/Hap 2, in MDR3 were closely associated with the susceptibility to jaundice-type progression of PBC [P = 0.004, odds ratio (OR) 3.93, 95% confidence interval (CI) 1.56-9.90 and P = 0.0003, OR 17.73, 95% CI 3.77-83.42, respectively]. Conversely, another haplotype, Hap 1, and its homozygous diplotype, Hap 1/Hap 1, were associated with the insusceptibility to the progression to late-stage PBC (P = 0.021, OR 0.55, 95% CI 0.33-0.91 and P = 0.011, OR 0.24, 95% CI 0.08-0.71, respectively). Conclusion: The present study is the first report of an association of MDR3 haplotypes and diplotypes with progression of PBC. The Hap 2/Hap 2 diplotype in MDR3 could therefore be potentially applied to DNA-based diagnosis in Japanese patients with PBC as a strong genetic biomarker for predicting the progression and prognosis of PBC.
University of NagasakiNagasaki, Nagasaki, Japan
Nagai Internal Medicine ClinicOkayama, Okayama, Japan
Osaka City University
Ōsaka, Ōsaka, Japan
- Second Department of Internal Medicine
Nagasaki University HospitalNagasaki, Nagasaki, Japan
Sasebo City General HospitalNagasaki, Nagasaki, Japan
Nagasaki-shi, Nagasaki-ken, Japan
- School of Medicine