Insong Koh

Sogang University, Seoul, Seoul, South Korea

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Publications (23)58.86 Total impact

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    ABSTRACT: Endoplasmic reticulum (ER) stress has recently been observed to activate NF-kappaB and induce inflammatory responses such as asthma. Activating transcription factor 6β (ATF6B) is known to regulate ATFα-mediated ER stress response. The aim of this study is to investigate the associations of ATF6B genetic variants with aspirin-exacerbated respiratory disease (AERD) and its major phenotype, % decline of FEV1 by aspirin provocation. Four common single nucleotide polymorphisms (SNPs) of ATF6B were genotyped and statistically analyzed in 93 AERD patients and 96 aspirin-tolerant asthma (ATA) as controls. Logistic analysis revealed that 2 SNPs (rs2228628 and rs8111, P=0.008; corrected P=0.03) and 1 haplotype (ATF6B-ht4, P=0.005; corrected P=0.02) were significantly associated with % decline of FEV1 by aspirin provocation, whereas ATF6B polymorphisms and haplotypes were not associated with the risk of AERD. Although further functional and replication studies are needed, our preliminary findings suggest that ATF6B may be related to obstructive phenotypes in response to aspirin exposure in adult asthmatics.
    Allergy, asthma & immunology research 03/2014; 6(2):142-8. · 2.65 Impact Factor
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    ABSTRACT: The aim of this study was to identify polymorphisms and gene-gene interactions that are significantly associated with age at menarche and age at menopause in a Korean population. A total of 3,452 and 1,827 women participated in studies of age at menarche and age at natural menopause, respectively. Linear regression analyses adjusted for residence area were used to perform genome-wide association studies (GWAS), candidate gene association studies, and interactions between the candidate genes for age at menarche and age at natural menopause. In GWAS, four single nucleotide polymorphisms (SNPs; rs7528241, rs1324329, rs11597068, and rs6495785) were strongly associated with age at natural menopause (lowest P = 9.66 × 10). However, GWAS of age at menarche did not reveal any strong associations. In candidate gene association studies, SNPs with P < 0.01 were selected to test their synergistic interactions. For age at natural menopause, there was a significant interaction between intronic SNPs on ADAM metallopeptidase with thrombospondin type I motif 9 (ADAMTS9) and SMAD family member 3 (SMAD3) genes (P = 9.52 × 10). For age at menarche, there were three significant interactions between three intronic SNPs on follicle-stimulating hormone receptor (FSHR) gene and one SNP located at the 3' flanking region of insulin-like growth factor 2 receptor (IGF2R) gene (lowest P = 1.95 × 10). Novel SNPs and synergistic interactions between candidate genes are significantly associated with age at menarche and age at natural menopause in a Korean population.
    Menopause (New York, N.Y.) 09/2013; · 3.08 Impact Factor
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    ABSTRACT: Lipoprotein lipase (LPL) plays an essential role in the regulation of high-density lipoprotein cholesterol (HDLC) and triglyceride levels, which have been closely associated with cardiovascular diseases. Genetic studies in European have shown that LPL single-nucleotide polymorphisms (SNPs) are strongly associated with lipid levels. However, studies about the influence of interactions between LPL SNPs and lifestyle factors have not been sufficiently performed. Here, we examine if LPL polymorphisms, as well as their interaction with lifestyle factors, influence lipid concentrations in a Korean population. A two-stage association study was performed using genotype data for SNPs on the LPL gene, including the 3' flanking region from 7,536 (stage 1) and 3,703 (stage 2) individuals. The association study showed that 15 SNPs and 4 haplotypes were strongly associated with HDLC (lowest p = 2.86 × 10(-22)) and triglyceride levels (lowest p = 3.0 × 10(-15)). Interactions between LPL polymorphisms and lifestyle factors (lowest p = 9.6 × 10(-4)) were also observed on lipid concentrations. These findings suggest that there are interaction effects of LPL polymorphisms with lifestyle variables, including energy intake, fat intake, smoking, and alcohol consumption, as well as effects of LPL polymorphisms themselves, on lipid concentrations in a Korean population.
    Genomics & informatics. 06/2012; 10(2):88-98.
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    ABSTRACT: Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) plays a role in the 5-lipoxygenase (LO) pathway, which includes the LTC(4), LTD(4), LTE(4) and LTB(4). These leukotrienes are known causative factors of asthma, allergy, atopy and cardiovascular diseases. ALOX5AP lacks enzyme activity and acts by helping 5-LO function. In this study, healthy and general subjects who live in rural and urban areas of Korea were tested for the association of ALOX5AP polymorphisms with lung function. Lung function was also estimated by calculating the predicted values for forced expiratory volume in one second (FEV(1) _%PRED) and the proportion of the forced vital capacity exhaled in the first second (FEV(1) /FVC_PRED). The linear regression was adjusted for residence area, gender, age, height and smoking status. The analysis revealed associations between FEV(1) and the single-nucleotide polymorphism (SNP) rs9506352 and the haplotype TCAC (permuted P-value < 0.05). The linkage disequilibrium block that included the significant SNPs overlapped with SNPs that were revealed previously to associate with myocardial infarction and asthma and to affect lung function. This study is the first to demonstrate the association between lung function and ALOX5AP polymorphisms in a healthy and general population.
    Scandinavian Journal of Immunology 04/2012; 76(2):151-7. · 2.20 Impact Factor
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    ABSTRACT: Precise topographic localization, predominance in males mostly of Asian origin, and existence of some familial cases suggest a genetic background for monomelic amyotrophy. To identify susceptibility genes for monomelic amyotrophy, we performed whole-exome sequencing of four unrelated patients with monomelic amyotrophy and detected a total of 45 novel nonsynonymous single-nucleotide polymorphisms as unique variants to monomelic amyotrophy compared to control exomes. Genetic association analysis showed significant association with monomelic amyotrophy in the Gly668Ser variant of the KIAA1377 gene (odds ratio=4.62, P-value=0.0040) and the Pro1794Leu variant of the C5orf42 gene (odds ratio=4.63, P-value=0.0040). Moreover, the combination of two variants increased the risk of monomelic amyotrophy (P=1.4×10(-5), OR=61.69, 95% confidence interval=9.62-394.94, in case of combination of two heterozygotes). These data suggest that KIAA1377 and C5orf42 synergistically play a role as susceptibility genes for monomelic amyotrophy.
    Neuromuscular Disorders 01/2012; 22(5):394-400. · 3.46 Impact Factor
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    ABSTRACT: Airway remodeling and exacerbated airway narrowing in asthma have been attributed to the regulation of intracellular Ca(2+) by sarcoplasmic reticulum (SR) of the airway smooth muscle cells. The protein encoded by obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF (OBSCN) is a crucial factor in determining the SR architecture in Obscn(-/-) mice. This study genotyped a total of 55 common single-nucleotide polymorphisms (SNPs) in 592 Korean asthmatics including 163 aspirin exacerbated respiratory disease (AERD) cases and 429 aspirin-tolerant asthma (ATA) controls. Eight SNPs, including two nonsynonymous polymorphisms rs1188722C>T (Leu2116Phe) and rs1188729G>C (Cys4642Ser), and one haplotype BL2_ht1 showed statistically significant associations with AERD development (p=0.003-0.03). Two variants, rs1188722C>T (Leu2116Phe) and rs369252C>A, also revealed nominal association with FEV1 decline by aspirin provocation in asthmatics (p=0.03-0.04). Intriguingly, rs1188722C>T (Leu2116Phe) is a highly conserved amino acid residue among species, suggesting its functional relevance to AERD. In addition, the A allele of rs369252C>A, which was more prevalent in AERD than in ATA, was predicted as a potential branch point (BP) site for alternative splicing (BP score=4.29). Although further functional evaluation is required, our findings suggest that OBSCN polymorphisms, in particular, highly conserved nonsynonymous Leu2116Phe variant, might contribute to aspirin hypersensitivity in asthmatics.
    DNA and cell biology 01/2012; 31(6):1001-9. · 2.28 Impact Factor
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    ABSTRACT: 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.
    Journal of Molecular Neuroscience 11/2011; 46(3):688. · 2.89 Impact Factor
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    ABSTRACT: The RecA homolog, E. coli (S. cerevisiae) (RAD51) may modulate hepatitis B virus (HBV) infection by maintaining genome integrity and mediating homologous DNA repairs. In this study, 16 sequence variations were detected by resequencing all exons, the exon-intron boundary, and promoter regions of the human RAD51 gene in DNA samples of 24 unrelated individuals. To investigate the association of common variations in the RAD51 locus with HBV infection and hepatocellular carcinoma (HCC) occurrence, six common polymorphisms were genotyped in a total of 1,103 Korean HBV cohort, composed of 433 spontaneously recovered patients as controls and 670 chronic carriers of HBV, who were stratified further into 327 cirrhosis/chronic hepatitis patients and 343 patients with HCC infected with HBV. Logistic analyses revealed no significant association of RAD51 polymorphisms and haplotypes with HBV clearance and HCC occurrence (P > 0.05). Furthermore, with age of infection as an important factor in disease progression to HCC, results from the Cox proportional hazards analysis showed no significant associations between any of the tested RAD51 variants and the age of onset of HCC (P > 0.05), suggesting that genetic polymorphisms of RAD51 may not play an important role in clearance of HBV and disease progression to HCC. Although studies in other populations are needed to confirm these findings, this preliminary data may contribute to the current knowledge on the pathogenesis of hepatitis.
    Journal of Medical Virology 11/2011; 83(11):1892-9. · 2.37 Impact Factor
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    ABSTRACT: Height is a highly heritable trait that involves multiple genetic loci. To identify causal variants that influence stature, we sequenced whole exomes of four children with idiopathic short stature. Ninety-five nonsynonymous single-nucleotide polymorphisms (nsSNPs) were selected as potential candidate variants. We performed association analysis in 740 cohort individuals and identified 11 nsSNPs in 10 loci (DIS3L2, ZBTB38, FAM154A, PTCH1, TSSC4, KIF18A, GPR133, ACAN, FAM59A, and NINL) associated with adult height (P < 0.05), including five novel loci. Of these, two nsSNPs (TSSC4 and KIF18A loci) were significant at P < 0.05 in the replication study (n = 1,000) and five (ZBTB38, FAM154A, TSSC4, KIF18A, and FAM59A loci) were significant at P < 0.01 in the combined analysis (n = 1,740). Together, the five nsSNPs accounted for approximately 2.5% of the height variation. This study demonstrated the utility of next-generation sequencing in identifying genetic variants and loci associated with complex traits.
    Human Genetics 09/2011; 131(3):471-8. · 4.63 Impact Factor
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    ABSTRACT: 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.
    Journal of Molecular Neuroscience 08/2011; 46(3):476-82. · 2.89 Impact Factor
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    ABSTRACT: Aim:  The human adenosine diphosphate ribosyl transferase (ADPRT) gene might significantly affect cancer by encoding poly(ADP-ribose) polymerase 1 enzyme (PARP-1) and promoting an important role in cellular responses to DNA damage, genomic stabilization and regulation of tumor suppressor genes. We explored whether polymorphisms of ADPRT affect clearance of hepatitis B virus (HBV) infection or risk of hepatocellular carcinoma (HCC) occurrence in a Korean HBV cohort.Methods:  Genotyping was performed in a total of 1066 subjects composed of 434 spontaneously recovered (SR) subjects as normal controls and 632 chronic carriers (CC) of HBV who were further classified into 325 patients with liver cirrhosis (LC)/chronic hepatitis (CH) and 307 patients with HCC.Results:  Logistic analyses of six common single nucleotide polymorphisms (SNP) and their haplotypes revealed that none of the polymorphisms were significantly associated with clearance of HBV infection and HCC occurrence, except for nominal evidence of association between haplotype 2 (ht2) with HBV clearance (P = 0.05). In the analysis of age of HCC occurrence which is an important factor in disease progression to HCC, results from Cox proportional hazards showed that none of the variants were significantly associated with onset age of HCC occurrence, although a nominal signal in ht4 (P = 0.03, but Pcorr > 0.05) was initially detected.Conclusion:  Although ADPRT is an important gene for cellular responses and tumor regulations, our study provides evidence that ADPRT variations do not affect HBV clearance and HCC occurrence.
    Hepatology Research 01/2011; 41(3):250 - 257. · 2.07 Impact Factor
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    ABSTRACT: Schizophrenia is a multifactorial disorder and smooth pursuit eye movement (SPEM) disturbance is proposed as one of the most consistent neurophysiological endophenotype in schizophrenia. The aim of this study was to examine the genetic association of RANBP1 polymorphisms with the risk of schizophrenia and with the risk of SPEM abnormality in schizophrenia patients in a Korean population. Two SNPs of RANBP1 were genotyped by TaqMan assay. Their genetic effect of single/haplotype polymorphisms on the risk of schizophrenia and SPEM abnormality from 354 patients and 396 controls were performed using χ² and multiple regression analyses. Although no RANBP1 polymorphisms were associated with the risk of schizophrenia, a common haplotype, RANBP1-ht2 (rs2238798G-rs175162T), showed significant association with the risk of SPEM abnormality among schizophrenia patients after multiple correction (P(corr)  = 0.002-0.0003). The results of present study provide the evidence that RANBP1 on 22q11.21 locus might be causally related to the SPEM abnormality rather than the development of schizophrenia.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 01/2011; 156B(1):67-71. · 3.23 Impact Factor
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    ABSTRACT: Unlike Caucasian populations, genetic factors contributing to the risk of type 2 diabetes mellitus (T2DM) are not well studied in Asian populations. In light of this, and the fact that copy number variation (CNV) is emerging as a new way to understand human genomic variation, the objective of this study was to identify type 2 diabetes-associated CNV in a Korean cohort. Using the Illumina HumanHap300 BeadChip (317,503 markers), genome-wide genotyping was performed to obtain signal and allelic intensities from 275 patients with type 2 diabetes mellitus (T2DM) and 496 nondiabetic subjects (Total n = 771). To increase the sensitivity of CNV identification, we incorporated multiple factors using PennCNV, a program that is based on the hidden Markov model (HMM). To assess the genetic effect of CNV on T2DM, a multivariate logistic regression model controlling for age and gender was used. We identified a total of 7,478 CNVs (average of 9.7 CNVs per individual) and 2,554 CNV regions (CNVRs; 164 common CNVRs for frequency>1%) in this study. Although we failed to demonstrate robust associations between CNVs and the risk of T2DM, our results revealed a putative association between several CNVRs including chr15:45994758-45999227 (P = 8.6E-04, P(corr) = 0.01) and the risk of T2DM. The identified CNVs in this study were validated using overlapping analysis with the Database of Genomic Variants (DGV; 71.7% overlap), and quantitative PCR (qPCR). The identified variations, which encompassed functional genes, were significantly enriched in the cellular part, in the membrane-bound organelle, in the development process, in cell communication, in signal transduction, and in biological regulation. We expect that the methods and findings in this study will contribute in particular to genome studies of Asian populations.
    PLoS ONE 01/2011; 6(4):e19091. · 3.73 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the effects of aging and gender on the volumes of total brain, brainstem, cerebellum and lateral ventricle of healthy Koreans by magnetic resonance imaging (MRI). Using three-dimensional MRI volumetry, we compared the volumes of various brain regions according to age and gender in 115 healthy Koreans. There were significant differences in the volumes of midbrain, cerebellum and lateral ventricle, whereas those of brainstem and medulla showed no differences between old-age group and young-age group. Men have larger volume of medulla than women. Age-related differences in the volumes of total brain and pons were significantly larger in men than women.
    Brain research 05/2009; 1276:77-82. · 2.46 Impact Factor
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    ABSTRACT: In this paper, we propose new missing imputation methods for the missing genotype data of single nucleotide polymorphism (SNP). The common objective of imputation methods is to minimize the loss of information caused by experimental missing elements. In general, imputation of missing genotype data has used a major allele method, but this approach is not far from the objective of the imputation – minimizing the loss of information. This method generally produces high error rates of missing value estimation, since the characteristics of the genotype data are not considered over the structure of given genotype data. In our methods, we use the linkage disequilibrium and haplotype information for the missing SNP genotype. As a result, we provide the results of the comparative evaluation of our methods and major allele imputation method according to the various randomized missing rates.
    Inf. Sci. 01/2007; 177:804-814.
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    ABSTRACT: Growing evidence supports the hypothesis that chronic low-grade inflammation related to innate immunity may play an important role in the pathophysiology of Type 2 diabetes mellitus (T2DM). The monocyte differentiation antigen CD14 gene (CD14) acts as the receptor for lipopolysaccharide (LPS) and augments monocyte/macrophage inflammatory responses. We have sequenced the gene, including all exons, exon/intron boundaries, and the -1.5 kb of the 5' flanking region. Two common loci (minor allele frequency > 0.05) were genotyped in 775 T2DM patients and 316 control subjects recruited in the Korean T2DM Study. Eight polymorphisms, including four non-synonymous forms, were identified in CD14. No polymorphisms were found in association with T2DM. However, one common promoter SNP (-260T>C) was significantly associated with both the serum triglyceride level (TG) and body mass index (BMI) in non-diabetic control subjects. Individuals who carried the minor allele (C) had higher TG levels (1.65 +/- 0.81 vs. 1.46 +/- 0.80 mmol/l; P = 0.0007) and BMI (23.96 +/- 3.00 vs. 23.28 +/- 3.22 kg/m(2); P = 0.04) as compared with subjects carrying T/T genotypes. Our data suggest that lipid metabolism and obesity, important pathophysiological elements of T2DM and the metabolic syndrome, are regulated by complex mechanisms that include the CD14 gene polymorphism-mediated genetic propensity to non-specific inflammatory responses.
    Diabetic Medicine 02/2006; 23(1):72-6. · 3.24 Impact Factor
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    ABSTRACT: Numerous genetic studies have mapped asthma susceptibility genes to a region on chromosome 5q31-33 in several populations. This region contains a cluster of cytokines and other immune-related genes important in immune response. In the present study, to determine the genetic variations and patterns of linkage disequilibrium (LD), we resequenced all the exons and promoter regions of the 29 asthma candidate genes in the chromosome 5q31-33 region. We identified a total of 314 genetic variants, including 289 single nucleotide polymorphisms (SNPs), 22 insertion/deletion polymorphisms and 3 microsatellites. Standardized variance data for allele frequency revealed substantial differences in SNP allele frequencies among different ethnic groups. Interestingly, significant ethnic differences were observed mainly in intron SNPs. LD block analysis using 174 common SNPs with a frequency of >10% disclosed strong LD within most candidate genes. No significant LD was observed across genes, except for one LD block (CD14-IK block). Gene-based haplotype analyses showed that 1-5 haplotype-tagging SNPs may be used to define the six or fewer common haplotypes with a frequency of >5%, regardless of the number of SNPs. Overall, our results provide useful information for the identification of immune-mediated disease genes in the chromosome 5q31-33 region, as well as valuable evidence for gene-based haplotype analysis in disease association studies.
    International Archives of Allergy and Immunology 01/2006; 139(3):209-16. · 2.25 Impact Factor
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    ABSTRACT: The relationship between human body size and brain size is still controversial, although brain size increases with body size across taxonomic levels. The magnetic resonance imaging volumetric analysis of the brain was performed in healthy 20-year old Koreans to investigate the effect of body size on brain volume. The whole brain volume was significantly correlated with body height in male (r=0.37, P<0.05) but not in female participants. The height effect on whole brain volume was increased considerably when data from both male and female participants were combined (r=0.57, P<0.05). The cerebellum volume was moderately correlated with body height in female (r=0.43, P<0.05) but not in male participants. The difference between sexes of the effect of body size on the brain needs to be investigated further.
    Neuroreport 12/2005; 16(18):2029-32. · 1.40 Impact Factor
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    ABSTRACT: In an effort to identify genetic polymorphisms in potential candidate genes for type 2 diabetes mellitus (T2DM), we have sequenced the transforming growth factor beta-induced gene (TGFBI), and examined the association with T2DM and diabetic phenotypes in a Korean T2DM study (775 T2DM patients and 316 normal controls). Twenty-eight polymorphisms were identified in TGFBI. Although no significant associations were detected with the risk of T2DM, one SNP in intron 16 (c.2011+137C>T) and one SNP in the 3' untranslated region (UTR) (c.2589T>G), showed significant association with the levels of insulin and body mass index (BMI) among nondiabetic controls. The lower insulin and BMI were observed in individuals who carry one or two copies of minor alleles than others. For example, the highest BMI (24.21 kg/m(2)) in individuals with homozygote major alleles (T) of c.2589T>G (n=99), the intermediate BMI (23.68 kg/m(2)) in individuals with heterozygote alleles (n=156), and the lowest BMI (22.69 kg/m(2)) in individuals with homozygote minor alleles (G) (n=57, P=0.005) were observed. The present study provides, for the first time, information about genetic polymorphisms in TGFBI and positive associations of those polymorphisms with levels of insulin and BMI in the Korean population.
    Human Mutation 03/2005; 25(3):322. · 5.21 Impact Factor
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    ABSTRACT: Comparative Statistic Module(CSM) provides more reliable list of significant genes to genomics researchers by offering the commonly selected genes and a method of choice by calculating the rank of each statistical test based on the average ranking of common genes across the five statistical methods, i.e. t-test, Kruskal-Wallis (Wilcoxon signed rank) test, SAM, two sample multiple test, and Empirical Bayesian test. This statistical analysis module is implemented in Perl, and R languages.
    Genomics & informatics. 01/2005; 2:180-183.

Publication Stats

244 Citations
58.86 Total Impact Points

Institutions

  • 2011–2012
    • Sogang University
      • Department of Life Science
      Seoul, Seoul, South Korea
  • 2009–2012
    • Hanyang University
      • College of Medicine
      Sŏul, Seoul, South Korea
  • 2004–2007
    • National Human Genome Research Institute
      Maryland, United States
  • 2004–2005
    • National Institute of Health, Korea
      Seishō-gun, North Gyeongsang, South Korea