Association analysis of PDE4B polymorphisms with schizophrenia and smooth pursuit eye movement abnormality in a Korean population.

Schizophrenia is a debilitating mental disorder with a high heritability rate. Located on chromosome 1p31.3, the human cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B) gene has been considered as an important candidate gene for the risk of schizophrenia. Several genetic association studies reported the association between PDE4B polymorphisms and the risk of schizophrenia in Caucasian, African American, Indian, and Japanese populations. The aim of this study is to examine the association of PDE4B variations with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. A case-control association analysis was carried out by comparing the genotype distribution of eight PDE4B polymorphisms between 457 schizophrenia patients and 386 normal healthy subjects. Differences in the frequency distribution of PDE4B single nucleotide polymorphisms (SNPs) and haplotypes were analyzed by logistic regression analyses controlling for age as a covariate. Statistical analyses revealed nominal significant associations of rs1040716, rs472952, rs1321177, and rs2144719 with the risk of schizophrenia (p = 0.02~0.05). The rs11208756 polymorphism showed a nominal significant association with SPEM abnormality (p = 0.05). In a meta-analysis with Japanese and Korean populations, three SNPs (rs472952, rs1040716, and rs2180335) revealed significant associations with schizophrenia (meta-p value = 0.0038~0.019). Our results support previously reported association of PDE4B variations with schizophrenia in other populations. The findings in this study add a new evidence for the involvement of PDE4B gene in schizophrenia etiology.

Lack of association of the RTN4R genetic variations with risk of schizophrenia and SPEM abnormality in a Korean population.

This study examined the association of the reticulon 4 receptor (RTN4R) gene with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Although we failed to provide convincing evidence that RTN4R is associated with schizophrenia development and SPEM impairment, our findings may be useful for further genetic studies.

Model for end-stage liver disease, model for end-stage liver disease-sodium and Child-Turcotte-Pugh scores over time for the prediction of complications of liver cirrhosis.

BACKGROUND/AIMS: There has been no report concerning the predictive capability of each scoring system in determining the development of complications of liver cirrhosis such as variceal bleeding and/or hepatic encephalopathy. METHODS: We retrospectively studied 128 patients with liver cirrhosis [92 males; mean (standard deviation) 54.2 (11.2) years] admitted to our institution from March 2004 to April 2006. Seventy-three patients (57.0%, group 1) were admitted because of complications of cirrhosis and 55 patients (43.0%, group 2) were admitted for causes unrelated to complications of cirrhosis. We calculated values for model for end-stage liver disease (MELD), MELD-sodium (MELD-Na) and Child-Turcotte-Pugh (CTP) scores on admission and at 3 and 6 months before admission. Each delta score was defined as the difference in the scores of 3 and 6 months before admission. RESULTS: The relative risk for complications in the patients with DeltaMELD/3 months >/=1.35, DeltaMELD-Na/3 months >/=1.35 and DeltaCTP/3 months >/=1 was 2.05 [95% confidence intervals (CI) 1.47-2.85, P<0.01], 2.04 (95% CI 1.45-2.88, P<0.01) and 1.98 (95% CI 1.39-2.81, P<0.01) respectively. The area under the receiver-operating characteristic curves of DeltaMELD/3 months, DeltaMELD-Na/3 months and DeltaCTP/3 months for the occurrence of cirrhotic complications were 0.691, 0.694 and 0.722 respectively. A higher DeltaMELD/3 months (>/=1.35), DeltaMELD-Na/3 months (>/=1.35) and DeltaCTP/3 months (>/=1) was associated with decreased survival. CONCLUSIONS: Delta model for end-stage liver disease/3 months, DeltaMELD-Na/3 months and DeltaCTP/3 months were clinically useful parameters for predicting the occurrence of cirrhotic complications.

[The clinical usefulness of focally enhanced gastritis in Korean patients with Crohn's disease].

BACKGROUND/AIMS: Focally enhanced gastritis (FEG) has been suggested as a specific diagnostic marker for patients with Crohn's disease (CD). However, the usefulness of FEG for distinguishing CD from ulcerative colitis (UC) is uncertain and the incidence or prevalence of FEG for inflammatory bowel disease (IBD) patients in Korea has not been defined yet. In this study, we investigated the frequency of FEG and other gastric histological abnormalities in Korean patients with CD and UC. METHODS: We evaluated 37 patients with known CD, 43 patients with UC and 41 non-IBD control group; all underwent upper gastrointestinal endoscopy followed by biopsy from the antrum and the body. The pathology of the gastric biopsy specimens and the presence of Helicobacter pylori (H. pylori) were evaluated. FEG was characterized by a focal perifoveolar or periglandular inflammatory cell infiltrates. RESULTS: H. pylori positive gastritis was found in 10 of 37 (27.0%) of CD patients, in 16 of 43 (37.2%) of UC patients, and in 22 of 41 (53.7%) of non-IBD control group (p=0.054). In H. pylori-negative patients, FEG was found in 8 of 27 patients (29.6%) of CD patients, 6 of 27 (22.2%) patients with UC, and 2 of 9 (10.5%) of non-IBD control group (p=0.324). CONCLUSIONS: In H. pylori-negative patients, there was no statistically significant difference in the occurrence of FEG among CD, UC and control groups in Korea.

[Comparison of Helicobacter pylori eradication rate in patients with non-ulcer dyspepsia and peptic ulcer diseases according to proton pump inhibitors].

BACKGROUND/AIMS: Conflicting results have been reported whether patients with non-ulcer dyspepsia (NUD) respond differently to Helicobacter pylori (H. pylori) eradication treatment compared with patients with peptic ulcer diseases (PUD). The aim of this study was to evaluate any difference in H. pylori eradication rates between patients with NUD and PUD according to each proton pump inhibitor (PPI). METHODS: From September, 2004 to April, 2007, we retrospectively reviewed 2,297 patients with NUD (1,050 patients) or PUD (1,247 patients) infected with H. pylori. All patients received a standard 1 week triple therapy comprising of one of the five PPIs (pantoprazole, esomeprazole, omeprazole, lansoprazole, rabeprazole), clarithromycin and amoxicillin. The follow-up H. pylori test was performed 4 weeks after the completion of therapy. RESULTS: There was no significant difference in the eradication rates between the two groups. In comparison of eradication rates according to PPI, omeprazole- based triple therapy group showed higher eradication rate than other groups in patients with NUD, but not in patients with PUD. CONCLUSIONS: This study failed to show any difference in H. pylori eradication rate between patients with NUD and PUD. There is no convincing evidence that the eradication rate may be affected by different PPI.

[Effectiveness of 10 day-sequential therapy for Helicobacter pylori eradication in Korea].

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. Proton pump inhibitor (PPI)-based triple therapy is the most preferred regimen in clinical practice. However, a critical fall in the H. pylori eradication rate has been observed in the recent years. A novel 10 day-sequential therapy consists of five days of dual therapy followed by five days of triple therapy regimen has recently been described. We aimed to evaluate whether 10 day-sequential therapy eradicated H. pylori infection better than the PPI-based triple therapy in Korea. METHODS: 158 patients with proven H. pylori infection were randomized to receive either 10 day-sequential therapy (20 mg of omeprazole, 1.0 g of amoxicillin, each administered twice daily for the first 5 days, followed by 20 mg of omeprazole, 500 mg of clarithromycin, 500 mg of metronidazole, each administered twice daily for the remaining 5 days) or PPI-based triple therapy (20 mg of omeprazole, 1.0 g of amoxicillin, 500 mg of clarithromycin, each administered twice daily for 1 week). Outcome of eradication therapy was assessed 8 weeks after the cessation of treatment. RESULTS: Eradication rates of 10 day-sequential therapy and PPI-based triple therapy were 77.9% (60/77) and 71.6% (58/81) by intention to treat analysis, respectively (p=0.361). By per protocol analysis, eradication rates of 10 day-sequential therapy and triple therapy were 85.7% (60/70) and 76.6% (58/76), respectively (p=0.150). There were no significant differences in adverse event rates and treatment compliance between two groups. CONCLUSIONS: The 10 day-sequential therapy regimen failed to achieve significantly higher eradication rates than PPI-based triple therapy.

Maximal Inspiratory Pressure and Maximal Expiratory Pressure in Healthy Korean Children.

OBJECTIVE: To evaluate respiratory muscle strength in healthy Korean children in order to establish the criteria for normal reference values for future applications. In contrast with the other parameters for testing pulmonary function, normal values for respiratory muscle strength in healthy Korean children have not been assessed to date. METHODS: We conducted a complete survey of 263 students at Sinmyung Elementary School in Yangsan, Gyeongsangnam-do, and measured their height and body weight, performed pulmonary function tests, and evaluated maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) as measures of respiratory muscle strength. We excluded the subjects with respiratory or cardiovascular diseases that could affect the results. The subjects were children aged 8-12 years, and they consisted of 124 boys and 139 girls. RESULTS: The MIP and MEP values (mean±standard deviation) for the entire subject group were 48.46±18.1 cmH2O and 47.95±16 cmH2O, respectively. Boys showed higher mean values for MIP and MEP in every age group. Korean children showed lower mean values for MIP and MEP compared to those in previous studies conducted in other countries (Brazil and USA). CONCLUSION: Our results showed that boys generally have greater respiratory muscle strength than girls. We found a significant difference between the results of our study and those of previous studies from other countries. We speculate that this may be attributed to differences in ethnicity, nutrition, or daily activities.

Correction: Physiological Responses During the Lower Body Positive Pressure Supported Treadmill Test.

[This corrects the article on p. 851 in vol. 40, PMID: 27847715.].

Analysis of Pulmonary Function Test in Korean Patients With Duchenne Muscular Dystrophy: Comparison of Foreign and Korean Reference Data.

OBJECTIVE: To determine the abnormal pulmonary function value in Korean Duchenne muscular dystrophy (DMD) patients, we performed a comparative analysis of the patients' pulmonary function value expressed as % of the overseas reference data and Korean healthy children and adolescent reference data. METHODS: We performed pulmonary function test (PFT) in a total of 27 DMD patients. We compared the patients' FVC% and FEV1% of the overseas reference data with those of the Korean children and adolescent reference data. Also, we compared the patients' MIP% and MEP% of the prediction equation data with those of the Korean children and adolescent reference data. RESULTS: Age of the subjects ranged from 8 to 16 years (12.03±2.27 years). The mean maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and peak cough flow (PCF) were 36.93±9.5 cmH2O, 45.79±17.46 cmH2O, 1.4±0.43 L, 1.45±0.45 L, 1.40±0.41 L, and 206.25±61.21 L/min, respectively. The MIP%, MEP%, and FVC% of the Korean children and adolescent reference data showed statistically significant higher values than those of the prediction equation data. CONCLUSION: We observed a clear numeric difference between Korean DMD patients' pulmonary function value expressed as % of the overseas data and inland data. To perform a precise assessment of respiratory function and to determine appropriate respiratory therapy, pulmonary function values of Korean DMD patients should be interpreted taking into account the inland normal pulmonary function test data.

Investigating the potential genetic association between RANBP9 polymorphisms and the risk of schizophrenia.

Schizophrenia is a serious mental disorder that is affected by genetic and environmental factors. As the disease has a high heritability rate, genetic studies identifying candidate genes for schizophrenia have been conducted in various populations. The gene for human Ran­binding protein 9 (RANBP9) is a newly discovered candidate gene for schizophrenia. As RANBP9 is a small guanosine­5'­triphosphate­binding protein that interacts with the disrupted in schizophrenia 1 protein, it is considered to be an important molecule in the pathogenesis of schizophrenia. However, to date, no study has examined the possible association between the genetic variations of RANBP9 and the risk of schizophrenia. In the present study, it was hypothesized that RANBP9 variations may influence the risk of schizophrenia. In order to investigate the association between RANBP9 polymorphisms and the risk of schizophrenia and smooth pursuit eye movement (SPEM) abnormalities, a case­control association analysis was performed. Using a TaqMan assay, five single­nucleotide polymorphisms and an insertion/deletion variation within the start codon region of RANBP9 were genotyped. Five major haplotypes were identified in 449 patients with schizophrenia and 393 unrelated healthy individuals as controls (total, n=842). However, the association analyses revealed no associations between all genetic variants and schizophrenia and SPEM abnormality. To the best of our knowledge, this is the first study to investigate an association between RANBP9 polymorphisms and schizophrenia and SPEM abnormality. The findings of allele frequencies and association results in this study may aid in further genetic etiological studies in schizophrenia in various populations.

Use of pupil size to determine the effect of electromagnetic acupuncture on activation level of the autonomic nervous system.

Magnetic fields are widely considered as a method of treatment to increase the therapeutic effect when applied to acupoints. Hence, this study proposes a new method which creates significant stimulation of acupoints by using weak magnetic fields. We conducted this experiment in order to confirm the effect on the activation level of the autonomic nervous system by measuring pupil sizes in cases of stimulation by using manual acupuncture and electromagnetic acupuncture (EMA) at BL15. We selected 30 Hz of biphasic wave form with 570.1 Gauss. To confirm the biopotential by the magnetic flux density occurring in EMA that affected the activation of the autonomic nervous system, we observed the biopotential induced at the upper and the mid left and right trapezius. We observed a significant decrease in pupil size only in the EMA group (p < 0.05), thus confirming that EMA decreased the pupil size through activation of the parasympathetic nerve in the autonomic nervous system. Moreover, we confirmed that the amplitude of the biopotential which was caused by 570.1 Gauss was higher than ±20 µA. Thus, we can conclude that EMA treatment successfully activates the parasympathetic nerve in the autonomic nervous system by inducing a biotransformation by the induced biopotential.

Genetic association analysis of CNR1 and CNR2 polymorphisms with schizophrenia in a Korean population.

Located on 6q15 and 1p36.11, cannabinoid receptor 1 (CNR1) and cannabinoid receptor 2 (CNR2) genes are considered to be a positional and functional candidate gene for the development of mental disorders such as schizophrenia because CNR1 is known as a regulator of dopamine signaling in the hippocampus and the cerebral cortex. However, few genetic studies have been carried out to investigate an association of CNR1 and CNR2 polymorphisms and the risk of schizophrenia. In this study, although the result indicates that CNR1 and CNR2 variations are unlikely to influence schizophrenia susceptibility in a Korean population, the findings would provide meaningful information for further genetic studies.

Lack of association between DISC1 polymorphisms and risk of schizophrenia in a Korean population.

The DISC1 gene is considered to be a strong candidate gene for the development of schizophrenia. This study examines the association of DISC1 polymorphisms with schizophrenia in a Korean population. Although we fail to discover convincing evidence that DISC1 affects schizophrenia development, our findings may be useful for further genetic studies.

Lack of associations of neuregulin 1 variations with schizophrenia and smooth pursuit eye movement abnormality in a Korean population.

Schizophrenia is a serious and disabling mental disorder with a high heritability rate. The human neuregulin 1 (NRG1) on 8p12 has been implicated as a candidate gene for schizophrenia. However, controversial results of the associations of NRG1 polymorphisms with schizophrenia and related phenotypes have been reported. In this study, four NRG1 single nucleotide polymorphisms, three in the promoter region, and one nonsynonymous in coding region, were genotyped in a total of 825 subject including 435 schizophrenia cases and 390 normal controls of Korean ethnicity. Although logistic association analysis of NRG1 polymorphisms and haplotypes with schizophrenia showed a nominal association in rs4623364G > C (P = 0.04), the significance disappeared after corrections for multiple testing (corrected P > 0.05). Additional case/control and multiple regression analyses in schizophrenia patients using a method that measures the smooth pursuit eye movement (SPEM) function globally based on natural logarithmic values of the signal/noise ratio also showed no association between NRG1 variants and SPEM abnormality among patients with schizophrenia (P > 0.05). Despite the need for further replications in other cohorts, our findings provide additional supporting information that four variants in NRG1 investigated in this study may not be associated with schizophrenia and its related SPEM function in a Korean population.

Genetic association analysis of ERBB4 polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population.

The human receptor tyrosine-protein kinase erbB-4 (ERBB4) gene mediates neuregulin 1 (NRG1) signaling, and is involved in neuronal migration and differentiation. Despite the potential significance of ERBB4 in the development of schizophrenia, relatively few genetic studies for the association of ERBB4 with schizophrenia were performed in the populations including Ashkenazi Jews, Americans including Caucasians and African Americans, and Han Chinese. In this study, differences in ERBB4 variations were investigated to determine association with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Seven polymorphisms in ERBB4 gene were genotyped in 435 schizophrenia cases and 390 unrelated healthy controls. In order to investigate the relationship between ERBB4 and the risk of schizophrenia and SPEM abnormality, differences in SNP and haplotype distribution were analyzed using logistic and multiple regression analyses. However, we failed to replicate the associations reported by previous studies in other populations. Although statistically not significant, the tendency towards associations between ERBB4 polymorphisms and the risk of schizophrenia and SPEM abnormality in this study from a Korean population would be helpful for further genetic etiology studies in schizophrenia.