한국인 고혈압군에서 Apolipoprotein CII 유전자의 돌연변이 탐색 및 혈장 중성지방 농도와의 관련성

배준설,강병용,김기태,신정희,이정주 한국지질동맥경화학회 2001 韓國脂質學會誌 Vol.11 No.4

Haplotype Distribution of the b2-Adrenergic Receptor Gene in Korean Essential Hypertensives

배준설,강병용,이강오,윤태중,김재현,김기태 한국독성학회 2002 Toxicological Research Vol.18 No.3

In view of the effect of β₂-Adrenergic receptors (β₂-AR) as a risk factor for essential hypertension, we investigated the Fnu4HI and MnlI RFLPs of β₂-AR gene in the Korean patients with essential hypertension and normal controls. There were no significant differences in the allele and genotype of these polymorphisms between normotensive and essential hypertensive subjects. In ethnic comparison, the allele frequencies of these three sites contained Nde I RFLP reported the association with essential hypertension in Korean population previously, were very different from those of other ethnic populations studied. The significant linkage disequilibrium was detected only in hypertensive group between Nde I and Fnu4HI sites. The Fnu4HI RFLP was also significantly associated with plasma triglyceride (TG) level. Therefore, our results suggest that the significant association between Fnu4HI variation in the human β₂-AR gene and plasma TG level may reflect the potential role of human β₂-AR gene as one of the genetic components for cardiovascular risk.

Genome-Wide Association Study for the Identification of Novel Genetic Variants Associated with the Risk of Neuroblastoma in Korean Children

배준설,이지원,유정은,정제균,유건희,구홍회,송윤미,성기웅 대한암학회 2020 Cancer Research and Treatment Vol.52 No.4

Purpose Neuroblastoma (NB) is the most common extracranial solid tumor found in children. To identify significant genetic factors for the risk of NB, several genetic studies was conducted mainly for Caucasians and Europeans. However, considering racial differences, there is a possibility that genetic predispositions that contribute to the development of NB are different, and genome-wide association study has not yet been conducted on Korean NB patients. Materials and Methods To identify the genetic variations associated with the risk of pediatric NB in Korean children, we performed a genome-wide association analysis with 296 NB patients and 1,000 unaffected controls (total n=1,296) after data cleaning and filtering as well as imputation of non-genotyped single nucleotide polymorphisms (SNPs) using IMPUTE v2.3.2. Results After adjusting for multiple comparisons, we found 21 statistically significant SNPs associated with the risk of NB (pcorr < 0.05) within 12 genes (RPTN, MRPS18B, LRRC45, KANSL1L, ARHGEF40, IL15RA, L1TD1, ANO7, LAMA5, OR7G2, SALL4, and NEUROG2). Interestingly, out of these, 12 markers were nonsynonymous SNPs. The SNP rs76015112 was most significantly associated with the risk of NB (p=8.1E-23, pcorr=2.3E-17) and was located in the RPTN gene. In addition, significant nonsynonymous SNPs in ADGRE1 were found in patients with MYCN amplification (rs7256147, p=2.6E-05). In high-risk group, rs7256147 was observed as a significant SNP (p=5.9E-06). Conclusion Our findings might facilitate improved understanding of the mechanism of pediatric NB pathogenesis. However, functional evaluation and replication of these results in other populations are still needed.

한국인 집단에서 심방 나트륨 이뇨 펩티드 유전자에 존재하는 유전적 변이와 본태성 고혈압과의 관련성에 관한 연구

배준설(Joon Seol Bae),강병용(Byung Yong Kang),이강오(Kang Oh Lee),이승택(Seung-Taek Lee) 한국독성학회 2006 Toxicological Research Vol.22 No.2

Hypertension leads to major health problems in many industrialized countries, and multiple etiologic factors are involved in the pathogenesis of this disorder. The genetic components of the natriuretic peptide system might be involved in the pathogenesis of hypertension. In this regard, the atrial natriuretic peptide (ANP) gene has been proposed as a candidate hypertension gene. Therefore, we investigated the G1837A and C-664G polymorphisms of the ANP gene in 143 Korean normotensives and 118 hypertensives. There were no significant differences in the genotype and allele frequencies between the two groups. Although the frequencies in each of these polymorphisms were not significantly different between normotensives and hypertensives, our results provide additional ethnic information for linkage analysis and associated studies of this disorder with cardiovascular disease.

한국인 고혈압군에서 Apolipoprotein CII 유전자의 돌연변이 탐색 및 혈장 중성지방 농도와의 관련성

배준설 ( Bae Jun Seol ),강병용 ( Kang Byeong Yong ),김기태 ( Kim Gi Tae ),신정희 ( Sin Jeong Hui ),이정주 ( Lee Jeong Ju ) 한국지질동맥경화학회 ( 구 한국지질학회 ) 2001 韓國脂質學會誌 Vol.11 No.4

Objective: Hypertension is a multifactorial disease. Both genetic and environmental factors have been implicated in its etiology. High level of plasma triglyceride was suggested a risk factor for the development of cardiovascular disease. Human apolipopro

Genetic Analysis of Kallikrein-Kinin System in the Korean Hypertensives

강병용,배준설,Kang Oh Lee 한국통합생물학회 2004 Animal cells and systems Vol.8 No.1

The kallikrein-kinin system affects regulation of blood pressure, and genes encoding for the components of this system have been considered as good candidates for hypertension. To evaluate the relationship between genetic polymorphisms of candidate genes involved in this system and hypertension, we performed case-control studies using genetic markers in Korean normotensives and hypertensives, respectively. By association study, there was a marginal association with hypertension in AA genotype distribution of A1789G polymorphism in the hKLK1 gene (P = 0.0754). Thus, this genetic polymorphism may weakly contribute to the susceptibility to hypertension in Koreans. We also observed that significant linkage disequilibrium exists among three polymorphic sites in the hKLK1 gene studied, suggesting that the three genetic polymorphisms can be useful as genetic markers in clinical association studies. Further studies using larger sample sizes and more genetic markers will be needed to clarify genetic influence of kallikrein-kinin system for hypertension.

Mutation Screening of the Human Lipoprotein Lipase Gene in Korean Individuals with Essential Hypertension

Kang, Byung Yong,Bae, Joon Seol,Kim, Ki Tae,Lee, Kyung Ho,Shin, Jung Hee,Lee, Chung Choo 한국유전학회 2002 Genes & Genomics Vol.24 No.1

Lipoprotein lipase (LPL) is the key enzyme for the hydrolysis of the core triglycerides of chylomicrons and very low-density lipoproteins (VLDL). Numerous mutations displaying extensive molecular heterogeneity for the LPL gene have been reported so far. To investigate whether such mutations may be associated with essential hypertension, we screened for mutations of this gene using single-strand conformation polymorphism (SSCP) in 96 Korean subjects with essential hypertension and in 143 normotensive individuals. Two mutations in intron 3(CCA→TCA) and exon 9(TCA→TGA, Ser^447→Ter) of the LPL gene were identified by SSCP analysis. Although neither mutation showed any association with essential hypertension, the intron 3(CCA→ TCA) mutation was significantly associated with body mass index (Mann-Whitney U-test, P<0.05). Therefore, this mutation may be useful as a genetic marker for linkage analysis of diverse common diseases.

Association Analysis of TEC Polymorphisms with Aspirin-Exacerbated Respiratory Disease in a Korean Population

이진솔,배준설,박병래,정현섭,김정현,Jason Yongha Kim,남궁석,김지온,박춘식,신형두 한국유전체학회 2014 Genomics & informatics Vol.12 No.2

The tyrosine-protein kinase Tec (TEC) is a member of non-receptor tyrosine kinases and has critical roles in cell signalingtransmission, calcium mobilization, gene expression, and transformation. TEC is also involved in various immune responses,such as mast cell activation. Therefore, we hypothesized that TEC polymorphisms might be involved in aspirin-exacerbatedrespiratory disease (AERD) pathogenesis. We genotyped 38 TEC single nucleotide polymorphisms in a total of 592 subjects,which comprised 163 AERD cases and 429 aspirin-tolerant asthma controls. Logistic regression analysis was performed toexamine the associations between TEC polymorphisms and the risk of AERD in a Korean population. The results revealed thatTEC polymorphisms and major haplotypes were not associated with the risk of AERD. In another regression analysis for thefall rate of forced expiratory volume in 1 second (FEV1) by aspirin provocation, two variations (rs7664091 and rs12500534)and one haplotype (TEC_BL2_ht4) showed nominal associations with FEV1 decline (p = 0.03-0.04). However, theassociation signals were not retained after performing corrections for multiple testing. Despite TEC playing an important rolein immune responses, the results from the present study suggest that TEC polymorphisms do not affect AERD susceptibility. Findings from the present study might contribute to the genetic etiology of AERD pathogenesis.

한국인에서 Angiotensin II Type 2 Receptor 유전자에 존재하는 C3123A 다형성과 본태성 고혈압과의 관련성에 관한 연구

강병용,배준설,이강오 환경독성보건학회 2005 환경독성보건학회지 Vol.20 No.1

Renin-angiotensin system(RAS)은 혈압 조절에 중요한 역할을 수행하는 생리적 조절계로써, 이 system을 구성하는 유전자들의 이상은 본태성 고혈압의 발병과 유의하게 관련된 것으로 알려졌다. RAS의 주 요한 구성 성분인 angiotensin II는 2 종류의 수용체인 angiotensin II type 1 receptor(AT1R)와 angiotensin IItype 2 receptor(AT2R)에 의해 그 효과가 매개되기 때문에, 이 수용체를 암호하는 유전자는 본태성 고혈압의 유력한 후보 유전자라고 볼 수 있다. 현재까지의 연구에 의하면, AT1R유전자에 존재하는 유전적 변이와 본태성 고혈압과의 관련성에 관해서는 많은 보고들이 있었지만, AT2R 유전자에 존재하는 유전적 변이.이에 본 연구에서는 한국인 집단을 대상으로 하여, AT2R 유전자에 존재하는 C3123A 다형성이 한국인 집단에서 본태성 고혈압과 유의한 관련성이 있는 지를 분석하였다. 이 유전자는 인간의 X 염색체에 존재하기 대문에, 여성인 경우에는 CC, CA 및 AA로 이루어진 3 유전자형이 존재하지만, 남성인 경우에는 C와A로 이루어진 2종류의 대립 유전자로 구성되어 있기 때문에, 본 연구에서는 남성과 여성을 개별적으로나누어서 분석하였다. 연구 결과, AT2R 유전자에 존재하는 C3123A 다형성은 남녀 모두에서 본태성 고혈압과 유의한 관련성을 나타내지 않았다(P¤ 0.05). 그렇지만, 집단과 비교했을 경우에는, 한국인을 대상으로 한 본 연구에서 A 대립 유전자 빈도가 0.33인 반면에 서양인 집단은 그 빈도가 0.43~ 0.48로 한국인 집단보다 높은 값을 나타내었다. 따라서, AT2R 유전자에 존재하는 C3123A 다형성과 본태성 고혈압과의 관련성에 대해서는 한국인과 유전적 배경이 다른서양인 집단을 대상으로 한 추시가 필요할 것으로 사료된다.

Absolute Neutrophil Count after the First Chemotherapy Cycle as a Surrogate Marker for Treatment Outcomes in Patients with Neuroblastoma

이지원,배준설,김진호,조희원,주희영,유건희,구홍회,우숙영,김선우,성기웅 대한암학회 2022 Cancer Research and Treatment Vol.54 No.1

Purpose We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma. Materials and Methods The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed. Results An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC. Conclusion In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered. Purpose We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma.Materials and Methods The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed.Results An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC.Conclusion In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.