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Atherosclerosis is associated with various cardiovascular diseases (CVDs). Measurement of arterial stiffness using pulse wave velocity (PWV) enables assessment of atherosclerosis progression in individuals. The authors screened patients with asymptomatic atherosclerosis, based on the PWV findings, to evaluate appropriate early interventions and assess the efficacy of γ‐linolenic acid, Vitis vinifera extract, and acetyl‐L‐carnitine triple combination therapy in atherosclerosis prevention. This retrospective study analyzed the medical records of adult patients between March 2007 and April 2019, with presenting complaints of fatigue and lethargy. Among patients with vascular stiffness beyond their biological age on brachial‐ankle PWV (baPWV) testing, those with ≥80% compliance for three drugs were allocated to the experimental group. Those with compliance of <80% for any one drug were allocated to the control group to assess changes in arterial stiffness, fasting plasma glucose (FPG), lipid level, and blood pressure (BP). After 1 year of triple‐combination therapy, there were significant decreases in right and left baPWV (1537.16 ± 274.84 and 1519.00 ± 289.32 cm/s, respectively) as compared to baseline (1633.15 ± 271. 20 and 1598.64 ± 267.95 cm/s, respectively; p <.001). There was no difference in baPWV between sexes. Moreover, neither group showed significant changes in FPG and lipid levels. When triple‐combination therapy combining γ‐linolenic acid, V. vinifera extract, and acetyl‐L‐carnitine was administered to patients with high arterial stiffness relative to their age, as assessed by baPWV, the experimental group showed a decrease in arterial stiffness in both sexes. [ABSTRACT FROM AUTHOR]

Background: Group B Streptococcus (GBS) and Escherichia coli are leading causes of late‐onset sepsis (LOS) and bacterial meningitis in neonates and infants. This study aimed to describe clinical characteristics and outcomes of community‐acquired (CA) LOS caused by GBS and E. coli. Methods: A retrospective observational study was performed in three university hospitals in Korea. All infants aged <90 days who were diagnosed with GBS or E coli CA‐LOS from 2011 to 2017 were enrolled. Data on the clinical characteristics and outcomes of GBS and E. coli CA‐LOS were compared. Results: Forty GBS and 43 E. coli CA‐LOS cases were identified, which mostly (82/83) included term or near‐term infants. Meningitis was identified in 54.1% of GBS CA‐LOS cases and in 30.3% of E. coli CA‐LOS cases, and 88.4% of E. coli CA‐LOS cases involved urosepsis. Ten percent each of GBS and non‐uropathogenic E. coli (non‐UPEC) meningitis cases and all uropathogenic E. coli (UPEC) meningitis cases were diagnosed by pleocytosis without bacterial growth in the cerebrospinal fluid (CSF). Patients with non‐culture‐proven meningitis had lower CSF pleocytosis and protein levels and higher CSF/serum glucose ratios than patients with culture‐proven meningitis (P < 0.05 for all). One patient died of CA‐LOS, which was accompanied by meningitis with extended‐spectrum β‐lactamase‐producing non‐UPEC. Neurological complications developed in 22.5% of GBS CA‐LOS cases and in 2.3% of E. coli CA‐LOS cases. Conclusions: Neurological complications were frequently observed in GBS CA‐LOS cases, although no mortality was observed. Escherichia coli CA‐LOS generally developed as urosepsis, which caused non‐culture‐proven meningitis and had a favorable outcome. [ABSTRACT FROM AUTHOR]

Background: The benefits of implantable cardioverter‐defibrillators (ICDs) for the prevention of sudden cardiac arrest (SCA) are well established. However, a significant knowledge gap remains regarding current indications and utilization of ICDs in real‐world settings in Asia. Methods: Patients who underwent ICD implantation in South Korea from 2007 to 2015 were identified using the Health Insurance Review and Assessment Service database. We investigated trends in use of ICD for the prevention of SCA. Results: A total of 4649 ICDs were implanted during 9 years. ICDs were implanted in 1448 (31.2%) patients for primary prevention and in 3201 (68.8%) for secondary prevention. The proportion of ICDs for primary prevention increased from 6.1% in 2007 to 41.9% in 2015. Primary prevention was more frequent in older (≥40 years) recipients (34.4% vs. 14.6%, P < .0001). The rates of ICD implantation for primary prevention were highest for nonischemic dilated cardiomyopathy (55.1%) and lowest (9.7%) for inherited primary arrhythmia syndrome (IPAS). Conclusion: Our data showed a trend of progressively increasing rates of ICD implantation in Asia, especially for primary prevention of SCA. Primary prevention as an indication for ICD in patients with IPAS remained low. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Although serum cystatin C level is considered a more accurate marker of renal function in patients with liver cirrhosis, its prognostic efficacy remains uncertain. This study aimed to evaluate the prognostic efficacy of serum cystatin C level in patients with cirrhotic ascites. Methods: Patients with cirrhotic ascites from 15 hospitals were prospectively enrolled between September 2009 and March 2013. Cox regression analyses were performed to identify independent predictive factors of mortality and development of type 1 hepatorenal syndrome (HRS‐1). Results: In total, 350 patients were enrolled in this study. The mean age was 55.4 ± 10.8 years, and 267 patients (76.3%) were men. The leading cause of liver cirrhosis was alcoholic liver disease (64.3%), followed by chronic viral hepatitis (29.7%). Serum creatinine and cystatin C levels were 0.9 ± 0.4 mg/dL and 1.1 ± 0.5 mg/L, respectively. Multivariate analyses revealed that international normalized ratio and serum bilirubin, sodium, and cystatin C levels were independent predictors of mortality and international normalized ratio and serum sodium and cystatin C levels were independent predictors of the development of HRS‐1. Serum creatinine level was not significantly associated with mortality and development of HRS‐1 on multivariate analysis. Conclusion: Serum cystatin C level was an independent predictor of mortality and development of HRS‐1 in patients with cirrhotic ascites, while serum creatinine level was not. Predictive models based on serum cystatin C level instead of serum creatinine level would be more helpful in the assessment of the condition and prognosis of patients with cirrhotic ascites. [ABSTRACT FROM AUTHOR]

Aim We determined if differences in renal function, even within normal levels, influenced hippocampal volume (HCV) and cognition. Methods Cognitively normal (CN) and mild cognitive impairment (MCI) subjects with eGFR ≥ 60 ml/min/1.73m2 were selected from the ADNI database ( N = 1,269) and divided into three groups (eGFR 60-75, 75-90 and ≥90). Associations between eGFR, HCV and cognition scores were examined using regression methods, and random-coefficient models. The relationship between various factors, such as vascular burden and brain amyloid deposition, were investigated using path analysis. Results Higher eGFR was associated with larger HCVs and better cognition in all subjects at baseline. In MCI subjects, hippocampal atrophy in the eGFR ≥ 90 group progressed at just half the rate of the eGFR 75-90 group ( P = .006), and was also somewhat slower than the eGFR 60-75 group ( P = .08). A comprehensive path model linking eGFR, HCV and cognition, and integrating vascular burden and amyloid deposition, is proposed. Conclusions Higher renal function was associated with slower hippocampal atrophy and cognitive decline even within normal levels of renal function. This relationship was mediated mainly through cardiovascular risk burden and amyloid deposition. Further studies examining neuroinflammation are needed. Geriatr Gerontol Int 2017; 17: 1899-1906. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the hepatic metabolic alterations in nonalcoholic fatty liver disease (NAFLD) by using 1 H-MRS (proton magnetic resonance spectroscopy) with long echo time and to test the reproducibility of human study in an animal model. Liver biopsy is the gold standard for diagnosing NAFLD but with practical constraints. 1 H-MRS allows in vivo assessment of hepatocellular metabolism and has shown potential for biochemical differentiation in diffuse liver disease.Materials and Methods: In all, 32 subjects (11 patients with nonalcoholic steatohepatitis [NASH], 15 with simple steatosis [SS], and six healthy controls) were studied. For test reproducibility, 36 C57BL/6 mice, including 10 mice with streptozotocin-induced NASH, 15 with SS, and 11 high-fat diet controls, were studied. 1 H-MRS measurements at 3T and 4.7T MRI were performed on a localized voxel of the liver using PRESS sequence. Hepatic alanine (Ala), lactate+triglyceride (Lac+TG), and TG levels were compared between NASH, SS, and control groups using analysis of variance (ANOVA) tests. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristics (ROC) curve. The associations between metabolite levels and pathologic grades or NAFLD activity scores (NAS) were assessed using Pearson's correlation.Results: NASH patients had higher levels of Ala (P < 0.001), Lac+TG (P < 0.001), and TG (P < 0.05) than SS patients or controls. The AUROC curve to distinguish NASH from SS was 1.00 (95% confidence interval [CI] 1.00-1.00) for Ala and 0.782 (95% CI 0.61-0.96) for Lac+TG. Ala and Lac+TG concentrations were positively correlated with steatosis grade (Ala Pearson's r = 0.723; Lac+TG r = 0.446), lobular inflammation (Ala r = 0.513), and NAS (Ala r = 0.743; Lac+TG r = 0.474).Conclusion: 1 H-MRS is potentially useful for noninvasive diagnosis of NASH and simple steatosis by hepatic metabolite quantification.Level Of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1298-1310. [ABSTRACT FROM AUTHOR]

Objectives In this study, we aimed to determine the role of genetic variations within the zinc finger protein 804A ( ZNF804A) gene, a candidate for a psychosis risk-conferring gene, in the development of schizophrenia ( SZ) and bipolar disorder ( BP) in the Korean population. Methods A total of 921 patients with SZ, bipolar I ( BP-I) and II ( BP- II) disorder, and 502 control subjects participated in the study. Twenty-one tag single nucleotide polymorphisms ( SNPs) across the genomic region of ZNF804A and seven reference SNPs based on previous reports were genotyped. We applied logistic regression analyses under additive, dominant and recessive models. Results Fifteen of the 28 SNPs showed a nominally significant association with at least one diagnostic group. However, none of these associations remained significant after false discovery rate ( FDR) correction. As the trend of association was observed mostly in SZ and BP-I with similar patterns, we performed a post hoc analysis for the combined SZ and BP-I group. Five SNPs (rs2369595, rs6755404, rs10931156, rs12476147 and rs1366842) showed a significant association with an FDR-corrected P of <.05. Conclusions This study supports a possible role of ZNF804A in the common susceptibility of major psychoses, and identified additional candidate variants of the gene in the Korean population. [ABSTRACT FROM AUTHOR]

Background and Aim As a rare liver disease, little is known about autoimmune hepatitis ( AIH). This study investigated the clinical features and compared two diagnostic criteria of AIH in Korea. Methods A nationwide, multicenter, retrospective analysis was done of data of adult patients diagnosed with AIH from January 2005 to December 2009. Results The enrolled patients ( n = 343; mean age, 52.8 years; range, 19-87 years; 12% male, 88% female) met diagnostic criteria of AIH according to the revised original criteria ( n = 311) or the simplified criteria ( n = 250). At diagnosis, 30.6% were asymptomatic, 22.7% were cirrhotic, and 4.3% displayed hepatic decompensation. The positive results for anti-nuclear antibody, smooth muscle antibody, and anti-liver/kidney microsomal antibody were 94.2%, 23.0%, and 2.9%, respectively. Definite AIH and probable AIH according to the revised original criteria were 24.8% and 65.3%, respectively, while those according to the simplified criteria were 34.4% and 38.5%, respectively. The diagnostic sensitivity and positive predictive value of simplified criteria in comparison with the revised original criteria were 69.9% and 86.4%, respectively. As an initial therapy, corticosteroid (37.7%) or corticosteroid with azathioprine (36.8%) was administered. Remission, incomplete response, and treatment failure were noted with 85.7%, 10.5%, and 3.9% of patients, respectively. Conclusions Autoimmune hepatitis in Korea is mostly type I, showing a mean age of 53 years with comparable clinical features to other countries. The concordant rate of the two diagnostic criteria was rather low with modest sensitivity of the simplified criteria. Further studies on the validation of the diagnostic criteria are warranted. [ABSTRACT FROM AUTHOR]

Backgrounds/Aims Metastatic tumour antigen 1 ( MTA1) promotes angiogenesis by stabilizing hypoxia-inducible factor-1α ( HIF-1α), which is closely associated with frequent postoperative recurrence and poor survival in patients with HCC. In this study, we determined single nucleotide polymorphisms ( SNPs) in angiogenesis-related genes that are associated with MTA1 overexpression in HCC tissues. Methods A total of 376 patients with HCC who had received curative surgical resection or liver transplantation were enrolled (312/21/43; HBV/ HCV/ NBNC). MTA1 expression was determined via immunohistochemistry. Thirty-three common SNPs sites (frequency ≥5%) in the angiogenic protein gene that are closely connected to one another were selected, including MTA1, VEGF, HIF-1α, FGF-2, and IGF- II. Results Expression of MTA1 was detected in 120 HCC tissues (31%). An A allele at position IVS4-81G/A of the MTA1 gene ( P = 0.016) and the TT genotype at position +12916C of the VEGF gene ( P = 0.023) were significantly associated with MTA1 overexpression. However, the TT genotype at position −13021C ( P = 0.011) and the haplotypes CT- CT (−11228C; −13021C) of the IGF- II gene ( Pcor = 0.033) were more common in patients with MTA1-negative HCC. Using multivariate analysis, the A allele at IVS4-81G/A in MTA1 gene ( P = 0.015) and a T allele ( TT+ CT genotype) at −13021C in IGF- II ( P = 0.002) were independent risk factors in HCC recurrence after curative surgical resection. Conclusions The genetic polymorphisms IVS4-81G/A in MTA1 and +12916C in VEGF genes were correlated with MTA1 overexpression. The SNPs in MTA1 and IGF- II genes may be important risk factors for the recurrence of HCC. [ABSTRACT FROM AUTHOR]

Th2-dominated immune responses are believed to contribute to the pathogenesis of atopic dermatitis (AD). IL-4 and IL-13 are typical pleiotropic Th2 cytokines that play a central role in IgE-dependent inflammatory reactions. Single-nucleotide polymorphisms (SNPs) in IL-4 and IL-13 have been reported in patients with allergic disease from numerous countries. Gene-gene interactions among genes have been identified in patients with asthma, although negative results have been reported. To investigate the associations of SNPs in these genes and the interactions between these genes in AD, we genotyped 23 SNPs of the IL-4, IL-13, IL-4R, IL-13Rα1 and IL-13Rα2 genes for 1089 case-control samples (631 AD patients and 458 controls) and analysed the SNPs and haplotypes in these genes. We also searched for gene-gene interactions among these five genes. Our data identified an association between rs3091307 and rs20541 in the IL-13 gene and between rs2265753 and rs2254672 in the IL-13Rα1 gene and the AD phenotype. In particular, three of the four SNPs were especially predictive of the allergic type of AD (ADe), and the haplotype TCGG in the IL-13Rα1 gene showed significant association with AD, especially ADe. Furthermore, the combination of rs3091307 GG/ rs2265753 GG (IL-13/IL-13Rα1) conveyed a significantly higher risk for developing ADe. However, we did not identify any SNPs in the IL-4, IL-4R and IL-13Rα2 genes that were associated with AD. As IL-13Rα1 is most likely expressed in Th17 cells rather than in Th2 cells, these data suggest diversity in the classification of Th cells that needs to be verified in future studies. [ABSTRACT FROM AUTHOR]

Clinical studies, including twin studies, support the concept that the risk of atopic dermatitis (AD) may be mediated through skin-specific genes, rather than simply through systemic immune or atopy risk genes. The SPINK5 gene is expressed on epithelial surfaces and may provide protection against other allergenic serine proteases. Mutations in the SPINK5 gene result in Netherton syndrome, a disorder characterised by AD, ichthyosis, and elevated serum IgE levels. We genotyped 21 single nucleotide polymorphisms (SNPs) from the SPINK5 gene for 1090 case-control samples (631 patients with AD and 459 normal controls) and analysed the SNPs and haplotypes in this gene and also searched for gene-gene interactions between SPINK5 and the DEFB1 gene that we previously reported. Six SNPs [rs17718511 ( P = 0.026), rs17860502 ( P = 0.024), KN0001820 ( P = 0.045), rs60978485 ( P = 0.007), rs17718737 ( P = 0.02), and rs1422985 ( P = 0.038)] and the haplotype TAA (rs60978485, rs6892205, rs2303064; P = 0.023) in the SPINK5 gene showed significant different allelic or genotypic distributions between the AD group and the control group. We also found that four SNPs [rs17718511 ( P = 0.033), rs17860502 ( P = 0.031), rs60978485 ( P = 0.005), rs17718737 ( P = 0.023)] and the haplotype TAA ( P = 0.02) in the SPINK5 gene showed associations with the susceptibility of the allergic type of AD (ADe). In addition to this finding, we speculate that the SNPs from DEFB1 and SPINK5 affect the individual susceptibility to development of ADe in an additive manner. This study provides evidence for a significant interaction between allergens and the SPINK5 gene that may contribute to ADe susceptibility. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is widely known to develop more frequently in cirrhotic patients with a high expression of Hepatitis B virus X protein (HBx), which is controlled by the enhancer 1 (Enh1)/X-promoter. To examine the effect of the mutations in the Enh1/X-promoter region in hepatitis B virus (HBV) genomes on the development of HCC, we investigated the differences in HBV isolated from cirrhotic patients with or without HCC along with the promoter activities of certain specific mutations within the Enh1/X-promoter. We examined 160 hepatitis B surface antigen (HBsAg)-positive cirrhotic patients (80 HCC patients, 80 non-HCC patients) by evaluating the biochemical, virological, and molecular characteristics. We evaluated the functional differences in certain specific mutations within the Enh1/X-promoter. The isolated sequences included all of the subgenotypes C2. The sites that showed higher mutation rates in the HCC group were G1053A and G1229A, which were found to be independent risk factors through multiple logistic analysis ( P < 0.05). Their promoter activities were elevated 2.38- and 4.68-fold, respectively, over that of the wild type in the HepG2 cells. Similarly, both the mRNA and protein levels of HBx in these two mutants were much higher than that in wild type-transfected HepG2 cells. Mutated nucleotides of the Enh1/X-promoter, especially G1053A and G1229A mutations in the HBV subgenotype C2 of patients with cirrhosis, can be risk factors for hepatocarcinogenesis, and this might be due to an increase in the HBx levels through the transactivation of the Enh1/X-promoter. ( Cancer Sci 2010) [ABSTRACT FROM AUTHOR]

Specific mutations in the hepatitis B virus (HBV) genome have been reported to be associated with the development of hepatocellular carcinoma (HCC). The goal of this study was to determine whether mutations in the HBV X gene are associated with the development of HCC in hepatitis B patients with cirrhosis. Forty-two patients infected with HBV genotype C2 with cirrhosis and HCC were compared with 46 patients with cirrhosis but without HCC. X gene mutations were determined by direct sequencing in all patients. The HCC and non-HCC groups were similar with respect to clinical characteristics, and the presence of T1762/A1764, T1653, and V1753 mutations was not significantly different between the two groups (P = 0.068, P = 0.097, P = 0.442, respectively). Only the B1499 mutation was associated significantly with HCC (P = 0.015) (odds ratio: 3.42, 95% CI: 1.24-9.48). In hepatitis Be antigen (HBeAg)-positive patients, advanced age was associated significantly with HCC (P = 0.038), whereas in HBeAg-negative patients, the B1499 mutation was associated more significantly with HCC (P = 0.01). Patients in the B1499 mutation group exhibited significantly higher AST and ALT levels compared with patients infected the wild-type virus. In conclusion, B1499 is a novel mutation associated with HCC in Korean patients with cirrhosis infected with HBV genotype C2. J. Med. Virol. 81:1721-1725, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Simultaneous determination of lactic acid, pyruvic acid, 3-hydroxybutyric acid and acetoacetic acid for clinical monitoring of lactic acidosis and ketone body formation in human plasma (20 µL) was performed by gas chromatography-mass spectrometry in selected ion monitoring (SIM) mode after generating methoxime/tert-butyldimethylsilyl derivatives. All of the targeted carboxylic acids were detected by characteristic fragment ions, which permitted sensitive and selective identification in the presence of co-extracted free fatty acids and other acidic metabolites at much higher levels. The method was linear ( r ≥ 0.9991), reproducible (% relative standard deviation = 1.2-5.8), and accurate (% relative error = −7.2-7.6), with detection limits of 0.05-1.7 ng/mL. This rapid, accurate and selective method using minimal plasma samples (20 µL) is useful in the clinical monitoring of lactic acidosis and ketone body formation in plasma. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background & Aims: The aim of this study was to reveal nationwide seroprevalence of HCV infection in South Korea by a large-scale survey., Methods: From January to December 2009, a total of 291 314 adults underwent health check-up in 29 centres nationwide. The data concerning anti-HCV antibody and biochemical tests were obtained from all participants. Among subjects with positive anti-HCV, such data as HCV RNA, genotypes and treatment detail were additionally analysed., Results: Using an estimated 2009 population of Korea, the age, sex and area-adjusted anti-HCV positive rate was 0.78%. Anti-HCV prevalence in female patients (0.83%) was higher than that in male patients (0.75%). Gradual increase in anti-HCV positivity was observed, from 0.34% in those aged 20-29 years to 2.31% in those >70 years. The age- and sex-adjusted anti-HCV prevalence varied in different areas, being higher in Busan and Jeonnam (1.53-2.07%), mid-level in Seoul and surrounding districts (0.50-0.61%) and lower in Jeju (0.23%). The comparative analysis of laboratory variables between anti-HCV (+) and anti-HCV (-) group revealed significantly higher levels of alanine aminotransferase and lower levels of serum lipids in anti-HCV (+) group. Among 1 718 anti-HCV positive subjects, serum HCV RNA was measured only in 478 people, of whom 268 (56.1%) patients had detectable HCV RNA in serum. Among 50 patients for whom assessment of response to antiviral therapy was feasible, overall sustained virological response was achieved in 84% of patients., Conclusion: The prevalence of HCV infection is low in South Korea. Studies to analyse risk factors are warranted to reduce HCV infection., (© 2013 John Wiley & Sons A/S.)

Adverse effects of atypical antipsychotics (AAP) can include obsessive-compulsive (OC) symptoms. Based on biological evidence of the relationship between the glutamatergic system and both OC disorder and AAP, this study aimed to determine whether DLGAP3, coding a post-synaptic scaffolding protein of glutamatergic synapses, is associated with AAP-induced OC symptoms. Furthermore, we explored the interactions between DLGAP3 and a previously reported susceptibility gene, the glutamate transporter gene SLC1A1, regarding this phenotype. Subjects were clinically stable schizophrenia patients receiving AAP treatment (n = 94), and they comprised an OC group (n = 40) and a non-OC group (n = 54) (patients with and without AAP-induced OC symptoms, respectively). We performed allelic/genotypic/haplotype association analyses for seven tag single-nucleotide polymorphisms of DLGAP3 and gene-gene interaction analyses with rs2228622 of SLC1A1, observing a nominally significant association between AAP-induced OC symptoms and rs7525948 in both simple chi-square tests and the regression analyses (nominal P < 0.05). In the logistic regression analysis of gene-gene interaction, we found a significant interaction effect of rs7525948 of DLGAP3 and rs2228622 of SLC1A1 (permutation P = 0.036) on AAP-induced OC symptoms, with a 30.2 times higher odds for individuals carrying risk genotypes at both loci in comparison with the reference group, which had no risk genotypes. This study provides suggestive evidence that DLGAP3 and its interactive effect with SLC1A1 might be involved in susceptibility to developing OC symptoms in schizophrenia patients receiving AAP treatment., (Copyright © 2011 Wiley Periodicals, Inc.)

The present study reports the results of a genome-wide SNP linkage scan for schizophrenia in the Korean population. Fifty-six multiplex schizophrenia families were analyzed. Clinical evaluations on all subjects were consistently performed by raters in a single research team. Multipoint non-parametric linkage analysis was performed, and empirical simulations were generated to determine genome-wide significance. The authors found genome-widely significant evidence of linkage for schizophrenia to chromosomes 2p24.3 (NPL Z = 3.18) and 6q27 (NPL Z = 2.90). Six other chromosomal regions, that is, 3q24, 13q12.3, 18q22.3, 20p12.2, 4p14, and 1p36.12, yielded NPL Z scores of above 2.0 for either broad or narrow phenotype classes. Although linkage to these loci has not received prominent attention in studies on Caucasian families, multiple overlaps were observed between our loci (on 2p, 3q, and 13q) and linkage peaks generated from extended families in various isolated populations. Fine mappings and the detection of candidate genes within these regions are warranted., (2008 Wiley-Liss, Inc.)

Chromosome 1q contains a few loci for which modest evidence of linkage with schizophrenia has been reported in several independent studies. However, markers showing the peak linkage signal are dispersed over a large chromosomal region. In addition, inconsistent findings have been generated from different populations or different subgroups of the same populations. The purpose of the current study is to determine whether those loci are linked to schizophrenia in the Korean population. We investigated 46 Korean multiplex schizophrenia families, initially using 11 microsatellite markers spanning around 91 cM region of 1p22 approximately 42. In a non-parametric linkage analysis, D1S249 located on 1q32.1 showed statistical evidence suggestive of linkage. At the second stage analysis for narrowing down the region, four additional nearby markers were genotyped. In the single point analysis, we found another suggestive linkage signal at D1S2891. The highest NPL score of 2.67 (P = 0.0039) was obtained in the multi-point analysis. This study provides supportive evidence for linkage of chromosome 1q32 with schizophrenia., ((c) 2006 Wiley-Liss, Inc.)

Chromosome 8p21-12 has been reported to be a susceptibility locus for schizophrenia based on genome-wide linkage scans. After neuregulin 1 (NRG1) was identified as a positional candidate gene for schizophrenia in this locus, several independent association studies have reported controversial results. To determine whether genetic variations in this locus are associated with schizophrenia in the Korean population, we investigated multiplex families and unrelated patients using linkage and association analyses. Seven microsatellite markers in 8p21-12 were genotyped for 40 families with schizophrenia, and a non-parametric linkage analysis was applied. The association study was performed with 242 unrelated schizophrenia patients and the same number of normal controls for three single nucleotide polymorphisms (SNPs), two microsatellite markers and their haplotypes. A significant linkage signal was observed on D8S1769, which is located 352 kb upstream of the 5' end of the first exon of NRG1 for two ("narrow" and "narrow with auditory hallucination (AH)") of the three adopted phenotype classes. In the association study, the G allele of SNP8NRG241930 was significantly in excess in the subgroup of patients with AHs. We also found haplotypes which were associated with schizophrenia with a protective effect. This study provides additional suggestive evidence for both the linkage and association of genetic variations on 8p12, a locus of NRG1, with schizophrenia. NRG1 might either play a role in the predisposition to schizophrenia or be in linkage disequilibrium (LD) with a causal locus of this illness., (Copyright 2006 Wiley-Liss, Inc.)