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Jason Yongha Kim,
Jeong-Hyun Kim,
Byung-Lae Park, Charisse Flerida A Pasaje,
Joon Seol Bae,
Jong Sook Park,
An-Soo Jang,
Soo-Taek Uh,
Yong-Hoon Kim,
Mi-Kyeong Kim,
Inseon S Choi,
Sang Heon Cho,
Byoung Whui Choi,
Choon-Sik Park,
Hyoung Doo Shin
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ABSTRACT: Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1).
A total of 34 common FILIP1 single nucleotide polymorphisms (SNPs) were genotyped in 592 Korean asthmatic subjects that included 163 AERD patients and 429 aspirin-tolerant asthma (ATA) controls.
This study found that 5 SNPs (P=0.006-0.01) and 2 haplotypes (P=0.01-0.03) of FILIP1 showed nominal signals; however, corrections for the multiple testing revealed no significant associations with the development of AERD (P(corr)>0.05). In addition, association analysis of the genetic variants with the fall rate of FEV1, an important diagnostic marker of AERD, revealed no significant evidence (P(corr)>0.05).
Although further replications and functional evaluations are needed, our preliminary findings suggest that genetic variants of FILIP1 might be not associated with the onset of AERD.
Allergy, asthma & immunology research 01/2013; 5(1):34-41. · 1.91 Impact Factor
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ABSTRACT: Nasal polyps are abnormal lesions arising mainly from the nasal mucosa and paranasal sinuses. Since the human class II, major histocompatibility complex, transactivator (CIITA) is a positive regulator of class II, major histocompatibility complex gene transcription, the CIITA gene is thought to be involved in the presence of nasal polyps in asthma and aspirin hypersensitive patients. To investigate the association between CIITA and nasal polyposis, 18 single nucleotide polymorphisms (SNPs) were genotyped in 467 asthmatics who were classified into 158 aspirin-exacerbated respiratory disease (AERD) and 309 aspirin-tolerant asthma (ATA) subgroups. Differences in the frequency distribution of CIITA variations between polyp-positive cases and polyp-negative controls were determined using logistic analyses. Initially, a total of 9 CIITA variants were significantly associated with the presence of nasal polyps in the overall asthma, AERD and ATA groups [P=0.001-0.05, odds ratio (OR)=0.53-2.35 in the overall asthma group; P=0.01-0.02, OR=2.45-2.66 in the AERD group; P=0.001‑0.05, OR=0.45-2.61 in the ATA group using various modes of genetic inheritance]. One the variations (rs12932187) retained this association after multiple testing corrections (Pcorr=0.01) in the overall asthma group. In addition, two variations (rs12932187 and rs11074938) were associated with the presence of nasal polyps following multiple testing corrections (Pcorr=0.02 and 0.04, respectively) in the ATA group. These novel findings suggest that rs12932187 and rs11074938 may constitute susceptibility markers of inflammation of the nasal passages in asthma patients.
Molecular Medicine Reports 12/2012; · 0.42 Impact Factor
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Byung Lae Park,
Tae-Hoon Kim,
Jeong-Hyun Kim,
Joon Seol Bae, Charisse Flerida A Pasaje,
Hyun Sub Cheong,
Lyoung Hyo Kim,
Jong-Sook Park,
Ho Sung Lee,
Myung-Sin Kim,
Inseon S Choi,
Byoung Whui Choi,
Mi-Kyeong Kim,
Seungwoo Shin,
Hyoung Doo Shin,
Choon Sik Park
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ABSTRACT: Aspirin-exacerbated respiratory disease (AERD) is a nonallergic clinical syndrome characterized by a severe decline in forced expiratory volume in one second (FEV1) following the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin. The effects of genetic variants have not fully explained all of the observed individual differences to an aspirin challenge despite previous attempts to identify AERD-related genes. In the present study, we performed genome-wide association study (GWAS) and targeted association study in Korean asthmatics to identify new genetic factors associated with AERD. A total of 685 asthmatic patients without AERD and 117 subjects with AERD were used for the GWAS of the first stage, and 996 asthmatics without AERD and 142 subjects with AERD were used for a follow-up study. A total of 702 SNPs were genotyped using the GoldenGate assay with the VeraCode microbead. GWAS revealed the top-ranked variants in 3' regions of the HLA-DPB1 gene. To investigate the detailed genetic effects of an associated region with the risk of AERD, a follow-up targeted association study with the 702 single nucleotide polymorphisms (SNPs) of 14 genes was performed on 802 Korean subjects. In a case-control analysis, HLA-DPB1 rs1042151 (Met105Val) shows the most significant association with the susceptibility of AERD (p = 5.11 × 10(-7); OR = 2.40). Moreover, rs1042151 also shows a gene dose for the percent decline of FEV1 after an aspirin challenge (p = 2.82 × 10(-7)). Our findings show that the HLA-DPB1 gene polymorphism may be the most susceptible genetic factor for the risk of AERD in Korean asthmatics and confirm the importance of HLA-DPB1 in the genetic etiology of AERD.
Human Genetics 11/2012; · 5.07 Impact Factor
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ABSTRACT: The human WD repeat-containing protein 46 (WDR46; also known as C6orf11), located at the disease-relevant centromere side of the class II major histocompatibility complex region, is hypothesized to be associated with risk of aspirin-exacerbated respiratory disease (AERD) as well as a decline in forced expiratory volume in the first second (FEV1), an important diagnostic marker of asthma.
To investigate the association between WDR46 and AERD, five single-nucleotide polymorphisms (SNPs) were genotyped in 93 AERD cases and 96 aspirin-tolerant asthma controls of Korean ethnicity. Three major haplotypes were inferred from pairwise comparison of the SNPs, and one was included in the association analysis. Differences in the frequency distribution of WDR46 SNPs and haplotype were analyzed using logistic and regression models via various modes of genetic inheritance.
Depending on the genetic model, the logistic and regression analyses revealed significant associations between rs463260, rs446735, rs455567, rs469064, and WDR46_ht2 and the risk of AERD (P=0.007-0.04, P(corr)=0.01-0.04) and FEV1 decline after aspirin provocation (P=0.006-0.03, P(corr)=0.01-0.03). Furthermore, functional analysis in silico showed that the G>A allele of rs463260 located in the 5' untranslated region potentially matched a nucleotide sequence within an upstream open reading frame of WDR46.
These findings show for the first time that WDR46 is an important genetic marker of aspirin-induced airway inflammation and may be useful for formulating new disease-management strategies.
Allergy, asthma & immunology research 07/2012; 4(4):199-205. · 1.91 Impact Factor
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ABSTRACT: MicroRNAs have been recently identified as important regulators that influence human carcinogenesis, cancer progression, and the interaction between the host and virus. This study investigates an association between microRNAs (miR-101-1, miR-101-2, and miR-338) and the risk of liver diseases through clearance of hepatitis B virus infection, development of liver cirrhosis, and hepatocellular carcinoma occurrence.
Genetic variations were genotyped using the TaqMan assay in 1439 Korean hepatitis B virus patients. To investigate the relationship between four polymorphisms in three microRNAs and the disease phenotypes, differences in frequency distribution of variations were analysed using logistic and multiple regression analyses after adjusting for age and gender as covariates.
We find that the rs7536540 polymorphism in miR-101-1 is significantly associated with development of liver cirrhosis and hepatocellular carcinoma occurrence. In addition, rs12375841 and its unique haplotype (ht2) in miR-101-2 show significant association with clearance of hepatitis B virus infection.
To our knowledge, this is the first study to examine a relationship between the three microRNA genes and the risk of hepatitis B-related liver diseases. We expect that the findings in this study will be helpful to further genetic studies in the pathophysiology of hepatitis B virus-related liver diseases.
Digestive and Liver Disease 05/2012; 44(10):849-54. · 3.05 Impact Factor
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Joon Seol Bae, Charisse Flerida A Pasaje,
Byung-Lae Park,
Hyun Sub Cheong,
Jeong-Hyun Kim,
Jason Yongha Kim,
Joong-Gon Shin,
Chul Soo Park,
Bong-Jo Kim,
Cheol-Soon Lee,
Migyung Lee,
Woo Hyuk Choi,
Tae-Min Shin,
Jaewook Hwang,
Hyoung Doo Shin,
Sung-Il Woo
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ABSTRACT: 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.
Brain research 05/2012; 1466:146-51. · 2.46 Impact Factor
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Jason Yongha Kim,
Jeong-Hyun Kim,
Byung-Lae Park, Charisse Flerida A Pasaje,
Joon Seol Bae,
Soo-Taek Uh,
Yong-Hoon Kim,
Mi-Kyeong Kim,
Inseon S Choi,
Sang Heon Cho,
Byoung Whui Choi,
Jong Sook Park,
Choon-Sik Park,
Hyoung Doo Shin
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ABSTRACT: The discoidin domain receptor tyrosine kinase 1 (DDR1) is positioned within the major histocompatibility complex (MHC) region which plays an important role in the immune system. In addition, DDR1 has been elucidated to be downregulated during the epithelial-mesenchymal transition of bronchial epithelium.
To investigate the potential genetic associations between DDR1 and aspirin-exacerbated respiratory disease (AERD), this study conducted association studies of DDR1 single nucleotide polymorphisms (SNPs) with AERD and the obstructive symptom of forced expiratory volume in 1 s (FEV(1)) decline after aspirin provocation.
Nine common SNPs were genotyped in 93 AERD patients and 96 aspirin-tolerant asthma (ATA) controls. The genotype distributions of all loci were in Hardy-Weinberg equilibrium (HWE; p > .05). Results. In the results of logistic analyses using age, sex, smoking status, and atopy as covariates, DDR1 rs1264320 in the intronic region showed a potent association signal with FEV(1) decline by aspirin provocation in asthmatics of this study even after corrections for multiple testing (p = .003 and corrected p = .01). However, the variants of DDR1 were not significantly associated with the AERD development (corrected p > .05). On further comparison of FEV(1) decline by aspirin provocation between AERD and ATA, the variant rs1264320 was found to be associated with the FEV(1) decline of ATA rather than AERD.
Despite the need for further functional evaluations and replications, we conclude that DDR1 polymorphisms are not likely to contribute to predispositions of AERD, but may be potentially associated with FEV(1) decline by aspirin provocation in asthmatics.
Journal of Asthma 03/2012; 49(3):237-42. · 1.52 Impact Factor
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ABSTRACT: Nasal polyps are abnormal lesions that cause airway obstruction and can occur along with other respiratory diseases. On account of its association with aspirin exacerbated respiratory disease (AERD), the human discoidin, CUB and LCCL domain containing 2 (DCBLD2) is hypothesized to be a candidate gene for the development of nasal polyps in asthma patients.
A total of 12 single-nucleotide polymorphisms (SNPs) were genotyped in 467 Korean asthma patients who were stratified further into 108 AERD and 353 aspirin-tolerant asthma (ATA) subgroups. Five major haplotypes were inferred from pairwise comparison of the polymorphisms. The patients were matched to control for confounds, and differences in the frequency distribution of DCBLD2 SNPs and haplotypes were analyzed using logistic models via various modes of genetic inheritance.
Results reveal significant association of rs828618 and DCBLD2_ht1 with nasal polyposis in the overall asthma patients group (P = 0.006, P(corr) = 0.05). Interestingly, the strength of association were maintained in the ATA subgroup (P = 0.007, P(corr) = 0.06), and moderate correlation was detected in the AERD subgroup (P = 0.04-0.05, P(corr) > 0.05).
Although further replication and validation are needed, these findings suggest that DCBLD2 could be a potential marker and drug target for treatment of nasal polyposis in Korean asthma patients.
Beiträge zur Klinik der Tuberkulose 01/2012; 190(2):199-207. · 1.90 Impact Factor
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Jeong-Hyun Kim,
Byung-Lae Park, Charisse Flerida A Pasaje,
Yongha Kim,
Joon Seol Bae,
Jong Sook Park,
Soo-Taek Uh,
Yong-Hoon Kim,
Mi-Kyeong Kim,
Inseon S Choi,
Sang Heon Cho,
Byoung Whui Choi,
InSong Koh,
Choon-Sik Park,
Hyoung Doo Shin
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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: Since subepithelial fibrosis and protruded extracellular matrix are among the histological characteristics of polyps, the emilin/multimerin domain-containing protein 2 (EMID2) gene is speculated to be involved in the presence of nasal polyps in asthma and aspirin-hypersensitive patients.
To investigate the association between EMID2 and nasal polyposis, 49 single-nucleotide polymorphisms (SNPs) were genotyped in 467 asthmatics of Korean ancestry who were stratified further into 114 aspirin exacerbated respiratory disease (AERD) and 353 aspirin-tolerant asthma (ATA) subgroups. From pairwise comparison of the genotyped polymorphisms, 14 major haplotypes (frequency > 0.05) were inferred and selected for association analysis. Differences in the frequency distribution of EMID2 variations between polyp-positive cases and polyp-negative controls were determined using logistic analyses.
Initially, 13 EMID2 variants were significantly associated with the presence of nasal polyps in the overall asthma group (P = 0.0008-0.05, OR = 0.54-1.32 using various modes of genetic inheritance). Although association signals from 12 variants disappeared after multiple testing corrections, the relationship between EMID2_BL1_ht2 and nasal polyposis remained significant via a codominant mechanism (P corr = 0.03). On the other hand, the nominal associations observed between the genetic variants tested for the presence of nasal polyps in AERD (P = 0.003-0.05, OR = 0.25-1.82) and ATA (P = 0.01-0.04, OR = 0.46-10.96) subgroups disappeared after multiple comparisons, suggesting lack of associations.
These preliminary findings suggest that EMID2_BL1_ht2 may be a susceptibility marker of inflammation of the nasal passages among Korean asthma patients.
BMC Medical Genetics 01/2012; 13:2. · 2.33 Impact Factor
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Jeong-Hyun Kim,
Byung-Lae Park,
Hyun Sub Cheong, Charisse Flerida A Pasaje,
Joon Seol Bae,
Jong Sook Park,
Soo-Taek Uh,
Yong-Hoon Kim,
Mi-Kyeong Kim,
Inseon S Choi,
Byoung Whui Choi,
Choon-Sik Park,
Hyoung Doo Shin
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ABSTRACT: Nasal polyps, part of the aspirin triad symptoms, are edematous protrusions arising from the mucosa of the nasal sinuses. Although the causative factors and pathogenesis of the polyps are unknown, the significant effect of human leukocyte antigen-DR (HLA-DR) expression in nasal polyps and genetic associations of the major histocompatibility complex class II, DR alpha (HLA-DRA) with immune-mediated diseases have been revealed.
To investigate the associations of HLA-DRA polymorphisms with nasal polyposis in asthmatic patients and in aspirin-hypersensitive subgroups, 22 single nucleotide polymorphisms (SNPs) were genotyped in a total of 467 asthmatic patients including 158 nasal polyp-positive and 309 polyp-negative subjects.
Statistical analysis showed that four SNPs (p = 0.0005-0.02; Pcorr = 0.009-0.033) and one haplotype (p = 0.002; Pcorr = 0.029) were significantly associated with the presence of nasal polyposis in asthmatic patients. In further analysis, although significant signals disappeared after corrections for multiple testing, two HLA-DRA polymorphisms (rs9268644C>A, rs3129878A>C) were found to be potential markers for nasal polyp development in aspirin-tolerant asthma (p = 0.005 and 0.007, respectively) compared with the aspirin-exacerbated respiratory disease (p > 0.05) subgroup. In silico analysis predicted major "C" allele of rs14004C>A in 5'-untranslated region as a potential binding site for regulatory glucocorticoid receptor. In addition, sequence nearby rs1051336G>A is suspected to be a pyrimidine-rich element that affects mRNA stability.
Despite the need for replication in larger cohorts and/or functional evaluations, our findings suggest that HLA-DRA polymorphisms might contribute to nasal polyposis susceptibility in patients with asthma.
American Journal of Rhinology and Allergy 01/2012; 26(1):12-7.
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ABSTRACT: Modest effects of genes in various pathways are significant in the etiology of complex human diseases, including aspirin exacerbated respiratory disease (AERD). By functioning as a relevant component of respiratory processes, the human kinesin family member C1 (KIFC1) is hypothesized to play a role in AERD pathogenesis. A case-control analysis was carried out by comparing the genotype distribution of six KIFC1 single-nucleotide polymorphisms between 93 AERD cases and 96 aspirin-tolerant asthma controls in a Korean population. After controlling for confounds, logistic and regression models via various modes of genetic inheritance facilitated the association analysis. Initial results revealed significant association at 0.05 level of significance between several KIFC1 variations and AERD (P = 0.01-0.05, OR = 1.81-1.90) as well as fall rate of forced expiratory volume in the 1st second, an important diagnostic marker of airways constriction (P = 0.04-0.05). However, the signals were not deemed significant after multiple testing corrections (P (corr) > 0.05). Although the results do not support a major role of KIFC1 in AERD pathogenesis in a Korean asthma cohort, further replication and validation studies are required to clarify the current findings.
Molecular Biology Reports 12/2011; 39(5):5913-9. · 2.93 Impact Factor
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Jeong-Hyun Kim,
Byung-Lae Park, Charisse Flerida A Pasaje,
Joon Seol Bae,
Chul Soo Park,
Boseok Cha,
Bong-Jo Kim,
Migyung Lee,
Woo Hyuk Choi,
Tae-Min Shin,
Ihn-Geun Choi,
Jaeuk Hwang,
Insong Koh,
Sung-Il Woo,
Hyoung Doo Shin
Journal of Molecular Neuroscience 11/2011; 46(3):688. · 2.50 Impact Factor
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Charisse Flerida A Pasaje,
Jeong-Hyun Kim,
Byung-Lae Park,
Hyun Sub Cheong,
Joon Seol Bae,
Tae-Joon Park,
Jin-Sol Lee,
Yongha Kim,
Hyo-Suk Lee,
Insong Koh,
Yoon Jun Kim,
Hyoung Doo Shin
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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. · 2.82 Impact Factor
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Jeong-Hyun Kim,
Byung-Lae Park, Charisse Flerida A Pasaje,
Joon Seol Bae,
Chul Soo Park,
Boseok Cha,
Bong-Jo Kim,
Jae Won Kim,
Woo Hyuk Choi,
Tae-Min Shin,
Ihn-Geun Choi,
Jaeuk Hwang,
Sung-Il Woo,
Hyoung Doo Shin
Psychiatric genetics 09/2011; 22(3):153-4. · 2.33 Impact Factor
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ABSTRACT: The human ubiquitin protein ligase E3C (UBE3C) regulates airway inflammatory responses and is hypothesized to be associated with the presence of nasal polyps in asthma-related diseases. A total of 24 UBE3C single-nucleotide polymorphisms (SNPs) were genotyped in a 467 Korean asthma cohort that was stratified into more homogenous phenotypes of 114 aspirin-exacerbated respiratory disease subgroup and 353 aspirin-tolerant asthma (ATA) subjects. Association analysis revealed that 16 UBE3C SNPs were significantly associated with presence of nasal polyps in the overall asthma group (P=0.0008 and P(corr)=0.01; odds ratio (OR)=0.60). The strength of association from 10 polymorphisms was increased in the ATA subgroup (P=0.0002 and P(corr)=0.003; OR=0.49). In addition, UBE3C_ht1 was found to be consistently associated with nasal polyps in the overall asthmatics group (P=0.006) and the ATA phenotype (P=0.002; P(corr)=0.02) via a codominant mechanism. Our findings provide evidence that variations in UBE3C are potent genetic markers of nasal polyps development in Korean asthmatics and may contribute novel insights into the clinical relevance and potential involvement of UBE3C in respiratory deficiencies.
Journal of Human Genetics 09/2011; 56(11):797-800. · 2.57 Impact Factor
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Jeong-Hyun Kim,
Byung-Lae Park, Charisse Flerida A Pasaje,
Joon Seol Bae,
Chul Soo Park,
Boseok Cha,
Bong-Jo Kim,
Migyung Lee,
Woo Hyuk Choi,
Tae-Min Shin,
Ihn-Geun Choi,
Jaeuk Hwang,
Insong Koh,
Sung-Il Woo,
Hyoung Doo Shin
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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. · 2.50 Impact Factor
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Charisse Flerida A Pasaje,
Joon Seol Bae,
Byung-Lae Park,
Hyun Sub Cheong,
An-Soo Jang,
Soo-Taek Uh,
Mi-Kyeong Kim,
Jeong-Hyun Kim,
Tae-Joon Park,
Jin-Sol Lee,
Yongha Kim,
Choon-Sik Park,
Hyoung Doo Shin
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ABSTRACT: Exacerbation of asthma symptoms due to aspirin ingestion may lead to life-threatening lung failure. The adhesion molecule CD58 gene may play a crucial role in aspirin-exacerbated respiratory disease (AERD) pathogenesis by mediating the biological functions of asthma-inducing mechanisms including T helper cells, proinflammatory cytokines, and natural killer T cells.
This study aimed to investigate the association of CD58 variations with aspirin-induced bronchospasm in Korean asthma patients.
Seven single-nucleotide polymorphisms were selected for genotyping based on previously reported polymorphisms in the International HapMap database. Genotyping was carried out using TaqMan assay and 2 major haplotypes were obtained in 163 AERD cases and 429 aspirin-tolerant asthma controls. Frequency distributions of CD58 variations were analyzed using logistic and regression models.
Results showed that none of the analyzed CD58 single-nucleotide polymorphisms and haplotypes was significantly associated with AERD development and fall rate of FEV(1) by aspirin provocation, an important diagnostic marker of aspirin hypersensitivity.
This preliminary study suggests that CD58 does not affect AERD susceptibility in a Korean population, and may provide a new direction for future disease etiology.
Journal of Asthma 08/2011; 48(6):539-45. · 1.52 Impact Factor
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Jeong-Hyun Kim,
Byung-Lae Park, Charisse Flerida A Pasaje,
Joon Seol Bae,
Jong Sook Park,
Sung Woo Park,
Soo-Taek Uh,
Mi-Kyeong Kim,
Inseon S Choi,
Sang Heon Cho,
Byoung Whui Choi,
Choon-Sik Park,
Hyoung Doo Shin
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ABSTRACT: Aspirin exacerbated respiratory disease (AERD) induces bronchoconstriction in asthmatic patients characterized with a clinical condition of severe decline in forced expiratory volume in one second (FEV1) after ingestion of aspirin. Two genes consisting a heterodimer, transporter 1 and 2, ATP-binding cassette, sub-family B (MDR/TAP) (TAP1 and TAP2) within the major histocompatibility complex (MHC) region, have been implicated in immunodeficiency and bronchiectasis development. To investigate the associations of TAP1 and TAP2 genetic polymorphisms with AERD and phenotypic FEV1 decline, a total of 43 common single-nucleotide polymorphisms (SNPs) including 12 SNPs of TAP1 and 31 SNPs of TAP2 were genotyped in 93 AERD patients and 96 aspirin-tolerant asthma controls. Interestingly, regression analysis revealed that polymorphisms and haplotypes of TAP2 were associated with FEV1 decline by aspirin provocation (P=0.002-0.04), with about twofold decline rate of FEV1 in most of minor homozygotes compared with major homozygotes. In addition, nominal evidences of association between TAP2 and AERD development were observed (P=0.02-0.04). However, TAP1 polymorphisms showed no relations to both AERD and FEV1 decline after aspirin challenge (P>0.05). Although further functional evaluations and replications are required, our preliminary findings provide supporting information that variants of TAP2 might be predisposing factors for FEV1 decline-related symptoms.
Journal of Human Genetics 07/2011; 56(9):652-9. · 2.57 Impact Factor
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Joon Seol Bae,
Myung Hun Jung,
Boung Chul Lee,
Hyun Sub Cheong,
Byung Lae Park,
Lyoung Hyo Kim,
Jeong-Hyun Kim, Charisse Flerida A Pasaje,
Jin Sol Lee,
Kyoung Hwa Jung,
Young Gyu Chai,
Hyoung Doo Shin,
Ihn-Geun Choi
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ABSTRACT: Alcoholism, a chronic behavioral disorder characterized by excessive alcohol consumption, has been a leading cause of morbidity and premature death. This condition is believed to be influenced by genetic factors. As copy number variation (CNV) has been recently discovered in human genome, genomic diversity of human genome is more frequent than previously thought. Many studies have reported evidences that CNV is associated with the development of complex diseases. In this study, we hypothesized that CNV can predict the risk of alcoholism.
Using the Illumina HumanHap660W-Quad BeadChip (∼660 k markers), genome-wide genotyping was performed to obtain signal and allelic intensities from 116 alcoholic cases and 1,022 healthy controls (total n = 1,138) in a Korean population. To identify alcoholism-associated CNV regions, we performed a genome-wide association analysis, using multivariate logistic regression model controlling for age and gender.
We identified a total of 255,732 individual CNVs and 3,261 CNV regions (1,067 common CNV regions, frequency > 1%) in this study. Results from multivariate logistic regression showed that the chr20:61195302-61195978 regions were significantly associated with the risk of alcoholism after multiple corrections (p = 5.02E-05, p(corr) = 0.04). Most of the identified variations in this study overlapped with the previously reported CNVs in the Database of Genomic Variants (95.3%). The identified CNVs, which encompassed 3,226 functional genes, were significantly enriched in the cellular part, in the membrane-bound organelle, in the cell part, in developmental processes, in cell communication, in neurological system process, in sensory perception of smell and chemical stimulus, and in olfactory receptor activity.
This is the first genome-wide association study to investigate the relationship between common CNV and alcoholism. Our results suggest that the newly identified CNV regions may contribute to the development of alcoholism.
Alcoholism Clinical and Experimental Research 07/2011; 36(1):35-42. · 3.34 Impact Factor
