Genome-wide linkage analysis for ocular and nasal anthropometric traits in a Mongolian population

Sun-Wha Im,이미경,Ganchimeg Jargal,성주헌,Sung-il Cho,김종일,김현진,Jae-hyuk Yi 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.12

Anthropometric traits for eyes and nose are complex quantitative traits influenced by genetic and environmental factors. To date, there have been few reports on the contribution of genetic influence to these traits in Asian populations. The aim of this study was to determine the genetic effect and quantitative trait locus (QTL) of seven traits eyes- and nose-related anthropometric measurements in an isolated Mongolian population. Frontal and lateral photographs were obtained from 1,014 individuals (434 males and 580 females)of Mongolian origin. A total of 349 short tandem repeat markers on 22 autosomes were genotyped for each individual. Heritability estimates of the seven ocular and nasal traits, adjusted for significant covariates,ranged from 0.48 to 0.90, providing evidence for a genetic influence. Variance-component linkage analyses revealed 10 suggestive linkage signals on 5q34 (LOD = 3.2), 18q12.2 (LOD = 2.7), 5q15 (LOD = 2.0), 9q34.2 (LOD = 1.9), 5q34 (LOD = 1.9), 17q22(LOD = 1.9), 13q33.3 (LOD = 2.7), 1q36.22 (LOD =1.9), 4q32.1 (LOD = 2.1) and 15q22.31 (LOD = 2.9). Our study provides the first evidence that genetics influences nasal and ocular traits in a Mongolian population. Additional collaborative efforts will further extend our understanding of the link between genetic factors and human anthropometric traits.

A newly developed capture-based sequencing panel for genomic assay of lung cancer

Sun‑Wha Im,Jeesoo Chae,Se Song Jang,Jaeyong Choi,Jihui Yun,차수진,Nak‑Jung Kwon,Yoon Kyung Jeon,Yoohwa Hwang,Miso Kim,Tae Min Kim,Dong‑Wan Kim,Jong‑Il Kim,Young Tae Kim 한국유전학회 2020 Genes & Genomics Vol.42 No.7

Background The increase in genetic alterations targeted by specific chemotherapy in lung cancer has led to the need for universal use of more comprehensive genetic testing, which has highlighted the development of a lung cancer diagnostic panel using next-generation sequencing. Objective We developed a hybridization capture-based massively parallel sequencing assay named Friendly, Integrated, Research-based, Smart and Trustworthy (FIRST)-lung cancer panel (LCP), and evaluated its performance. Methods FIRST-LCP comprises 64 lung cancer-related genes to test for various kinds of genetic alterations including single nucleotide variations (SNVs), insertions and deletions (indels), copy number variations (CNVs), and structural variations. To assess the performance of FIRST-LCP, we compiled test sets using HapMap samples or tumor cell lines with disclosed genetic information, and also tested our clinical lung cancer samples whose genetic alterations were known by conventional methods. Results FIRST-LCP accomplished high sensitivity (99.4%) and specificity (100%) of the detection of SNVs. High precision was also achieved, with intra- or inter-run concordance rate of 0.99, respectively. FIRST-LCP detected indels and CNVs close to the expected allele frequency and magnitude, respectively. Tests with samples from lung cancer patients also identified all SNVs, indels and fusions. Conclusion Based on the current state of the art, continuous application of the panel design and analysis pipeline following up-to-date knowledge could ensure precision medicine for lung cancer patients.

Genome-wide linkage analysis for ocular and nasal anthropometric traits in a Mongolian population

Im, Sun-Wha,Kim, Hyun-Jin,Lee, Mi-Kyeong,Yi, Jae-Hyuk,Jargal, Ganchimeg,Sung, Joo-Hon,Cho, Sung-Il,Kim, Jong-Il Korean Society for Biochemistry and Molecular Bion 2010 Experimental and molecular medicine Vol.42 No.12

Anthropometric traits for eyes and nose are complex quantitative traits influenced by genetic and environmental factors. To date, there have been few reports on the contribution of genetic influence to these traits in Asian populations. The aim of this study was to determine the genetic effect and quantitative trait locus (QTL) of seven traits eyes- and nose-related anthropometric measurements in an isolated Mongolian population. Frontal and lateral photographs were obtained from 1,014 individuals (434 males and 580 females) of Mongolian origin. A total of 349 short tandem repeat markers on 22 autosomes were genotyped for each individual. Heritability estimates of the seven ocular and nasal traits, adjusted for significant covariates, ranged from 0.48 to 0.90, providing evidence for a genetic influence. Variance-component linkage analyses revealed 10 suggestive linkage signals on 5q34 (LOD = 3.2), 18q12.2 (LOD = 2.7), 5q15 (LOD = 2.0), 9q34.2 (LOD = 1.9), 5q34 (LOD = 1.9), 17q22 (LOD = 1.9), 13q33.3 (LOD = 2.7), 1q36.22 (LOD = 1.9), 4q32.1 (LOD = 2.1) and 15q22.31 (LOD = 2.9). Our study provides the first evidence that genetics influences nasal and ocular traits in a Mongolian population. Additional collaborative efforts will further extend our understanding of the link between genetic factors and human anthropometric traits.

OB-52 : Fatal death: Cord accident in late pregnancy

( Sun Wha Im ),( Gwang Jun Kim ) 대한산부인과학회 2014 대한산부인과학회 학술대회 Vol.100 No.-

목적: Intrauterine fetal death is public health problem as well as a staggering event personally. This is a retrospective study at a single center and aimed to review possible or probable causes of fetal deaths especially in terms of cord accidents. 방법: A total of 40 fetal deaths that we have experienced at Chung-Ang University Hospital from July 2006 to July 2014 were reviewed. Fetal death was defined as no visible heartbeat of fetus in uterus with ultrasonography at 20 weeks` gestation or older. We excluded fetal deaths before 20 weeks, termination of pregnancy due to fetal genetic or structural fatal anomalies and preterm nonviable delivery in consequence of preterm labor or premature rupture of membrane. The gestation period was categorized as intermediate and late: 20-27 weeks and 28 weeks and more, respectively. 결과: Intermediate group, 20-27 weeks Sixteen cases out of 40 were included in this period. Different causes of death were involved in this period: cord hypercoiling (N=1), twin (N=2), genetic abnormalities (N=1), major structural abnormalities (N=2), oligohydramnios (N=2) and maternal diseases (N=2). Late pregnancy group, 28 weeks and more Of 40 cases, 62.5 % (25 cases) were occurred in late pregnancy. Mean fetal body weight of them was 2.05 kg and the number of fetus classified as small for gestational age was 5. Cord problems were found in 9 cases: cord hypercoiling (N=5), nuchal or body cord (N=3) and cord knot (N=1). Other possible or probable causes were twin (N=5), genetic abnormalities (N=2) and major structural abnormalities (N=2). Eight cases were remained to be unidentified. 결론: Previous reports of cord hypercoiling were focused on the fetal death in the second trimester of pregnancy. Fetal death related to cord accidents in late pregnancy was known to be attributed to cord occlusion caused by nuchal or body cord and cord knots. As our results, however, cord hypercoiling is not a rare event in the late pregnancy and could be found in routine check ultrasonography. Therefore, physicians have to pay attention to cord hypercoiling in ultrasonographic examination in the late pregnancy and take care of the patient provided that she has it.

Soluble Programmed Death-1 as a Serum Marker of Poor Liver Function for Hepatocellular Carcinoma Patients

( Jung Wha Chung ),( Sanghyuk Im ),( Yun Suk Choi ),( Eun Sun Jang ),( Jin-wook Kim ),( Sook-hyang Jeong ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Programmed death-1 (PD-1) and its ligands have critical roles in regulating T-cell immunity and PD-1 is expressed on a wide variety of tumors. Apart from the membrane-bound form, there is circulating, soluble form of PD-1 (sPD-1). Pattern of serum level of sPD-1 and role of sPD-1 in hepatocellular carcinoma (HCC) has not reported yet. This study aimed to investigate the pattern of the serum levels of sPD-1 and its relationship with clinical factors in HCC patients. Methods: The serum level of sPD-1 was measured by ELISA using stored samples obtained from newly diagnosed 307 HCC patients from to in a tertiary hospital. The frequency of detectable sPD-1, and comparative analysis on the clinical difference between detectable and non-detectable group. Results: Among the 307 HCC patients, mean age was 60.3 years, 81.1% were male, 73.3% were HBsAg-positive, and 17.9% were classified to Child-Pugh class B or C. The serum sPD-1 was detected in 111 patients (36.2%) with median level of 400 pg/mL (range, 3~170,048 pg/mL). Compared to the sPD-1 non-detectable group (n=196), the sPD-1 detectable group (n=111) showed significantly higher proportion of female (26.1% vs. 17.3%), viral etiology (90.1% vs 78.6%), and Child-Pugh class B or C (26.1% vs 13.3%), higher level of mean bilirubin (1.3 vs 0.9 mg/dL), mean INR of prothrombin time (1.19 vs 1.12), and mean model for end-stage liver disease (MELD) score (5.91 vs 4.37). During mean follow-up period of 15.9 months, the survival was not different between the sPD-1 detectable and non-detectable group. Conclusions: Serum sPD-1 level is detectable in less than 40% of HCC patients with median level of 400 pg/mL, and it is positively associated with female sex, viral etiology, and poor liver function in HCC patients.

The Surveillance Rate and Its Impact on Early Diagnosis and Survival of Hepatocellular Carcinoma in South Korea

( Sanghyuk Im ),( Ju Hyun Lee ),( Chung Seop Lee ),( Beom Hee Kim ),( Jung Wha Chung ),( Eun Sun Jang ),( Jin-wook Kim ),( Sook-hyang Jeong ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: The regular surveillance for early diagnosis of hepatocellular carcinoma (HCC) is widely recommended for high risk patient, however, its performance is suboptimal in real-life setting. This study aimed to elucidate the rate of performing surveillance and its impacts on early diagnosis and survival in newly diagnosed HCC patients in South Korea. Methods: In this prospective cohort study, newly diagnosed 350 HCC patients were consecutively enrolled from Mar 2012 to Apr 2016. A structured questionnaire survey on the HCC surveillance status was conducted by attending physicians from each patient with informed consents. Adequate surveillance was defined as serum AFP and liver imaging tests with 6-12 months interval over >2 years. Results: The adequate surveillance was performed in 92 patients (26.3%, Group 1: semiannual 83.7%, annual 16.3%), while not in 258 patients (73.7%, Group 2). Age and male proportion were not different from the two groups, however, advanced cirrhosis (Child-Pugh class B/C) was more frequent in Group 2 (18.6%) than in Group 1 (8.7%, p=0.026). Group 1 showed higher proportion of early HCC (BCLC stage 0/A, 75%) than Group 2 (50.4%, p-value <0.001). Group 1 showed longer overall survival (43.4 Mo., 95% CI 40.8-45.9) compared to Group 2 (39.1 Mo., 95% CI 36.7-41.5, p=0.017). The multivariable Cox regression analysis showed that, advanced cirrhosis (HR 1.161, 95% CI 1.79-6.38), and early stage (HR 1.431, 95% CI 3.98-20.67) were independent predictors of overall survival, while regular surveillance was insignificant (HR 1.736, 95% CI 0.82-4.64). Conclusions: Adequate surveillance was performed in less than one third of newly diagnosed Korean HCC patients, in them, 75% of HCC detected at early stage, which may improve survival of those patients. Comprehensive efforts to optimize the surveillance program for the target population should be urgently established.

Significance of Alpha-fetoprotein Variation in the Surveillance for Hepatitis B Virus-related Hepatocellular Carcinoma

( Jung Wha Chung ),( Beom Hee Kim ),( Chung Seop Lee ),( Ju Hyun Lee ),( Sanghyuk Im ),( Eun Sun Jang ),( Sook-hyang Jeong ),( Jin-wook Kim ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: α-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance. Although AFP is periodically measured in real-world practice, most published literature on the performance of AFP-based HCC surveillance analyzed single representative values. Serial changes in AFP levels might indicate presence of HCC, but AFP levels might also fluctuate without HCC during the natural course of chronic hepatitis B virus (HBV) infection. The aim of this study was to determine whether information on the serial changes in AFP values may improve the test performance of AFP during surveillance for HBV-associated HCC. Methods: A retrospective cohort of 4582 HBV-associated chronic hepatitis patients received HCC surveillance by means of AFP and ultrasonography. Development of HCC was evaluated for mean follow- up duration of 4.6 years. A total of 43028 AFP measurements were analyzed by ROC analysis. Serial changes in AFP levels were assessed by difference from baseline values (AFPdiff_base), differences from immediately previous result (AFPdiff_prev), Standard deviation value of AFP (AFPsd), numbers of episodes when AFP increased by 10 ng/mL compared to previous measurement. Results: Baseline HBeAg positivity was 36.7% patients, and 32.3% of total showed liver cirrhosis clinically. During the median follow-up of 49 months, 80 cases of HCC were identified: the 10-y incidence was 4.1%. Baseline AFP was 17.7 ng/mL in HCC patients and 13.3 ng/mL in patients without HCC (P = 0.638). The ROC analysis showed that AFPsd showed best performance (AUC = 0.811), followed by numbers of AFP increase > 10 ng/mL (AUC = 0.734), both of which were significantly superior to AFP alone (AUC = 0.624), AFPdiff_prev (AUC = 0.600) or AFPdiff_base (AUC = 0.561). Conclusions: Consideration of previous levels of AFP significantly increases the performance of AFP in the surveillance of HBV-associated HCC.

Ethnic variability in the allelic distribution of pharmacogenes between Korean and other populations

Kim, In-Wha,Kim, Kyung Im,Chang, Hyeu-jin,Yeon, Bora,Bang, Seo-Jin,Park, Taesung,Kwon, Ji-sun,Kim, Sangsoo,Oh, Jung Mi Lippincott Williams Wilkins, Inc. 2012 Pharmacogenetics and genomics Vol.22 No.12

OBJECTIVE: We examined the differences in allele frequencies for pharmacogenes among the Korean (KOR), Chinese (CHB), Japanese (JPT), Caucasian (CEU), and Nigerian (YRI) populations. METHODS: Fifty-seven pharmacogenes were selected from the imputed Korean Association REsource and HapMap databases. Minor allele frequencies were analyzed using the sample size-modified single nucleotide polymorphism-specific fixation index (FST) and the &khgr;-test with Bonferroni’s correction. Geneset analysis was also carried out to identify pharmacogenes that have significantly different allele frequencies among the various populations tested. RESULTS: The KOR population was the most divergent group from the YRI population (FST: 0.079) but very similar to the CHB and JPT populations (FST: 0.003). VKORC1 showed a large population divergence in the KOR–YRI (0.439) comparison. CYP3A4 was also highly divergent in the KOR–YRI (FST: 0.361) comparison. The calcium signaling pathway gene set was divergent in all pairwise population comparisons. CONCLUSION: In terms of the 57 pharmacogenes studied, there were no significant differences among the KOR, CHB, and JPT populations. However, the YRI and CEU populations were significantly differentiated from the three Eastern Asian groups. Future pharmacogenomics studies can utilize the polymorphisms identified in this study, as these variants may have important implications for the selection of highly informative single nucleotide polymorphisms for future clinical trials.

Genome-Wide Association Study of Bone Mineral Density in Korean Men

Bae, Ye Seul,Im, Sun-Wha,Kang, Mi So,Kim, Jin Hee,Lee, Soon Hang,Cho, Be Long,Park, Jin Ho,Nam, You-Seon,Son, Ho-Young,Yang, San Deok,Sung, Joohon,Oh, Kwang Ho,Yun, Jae Moon,Kim, Jong Il Korea Genome Organization 2016 Genomics & informatics Vol.14 No.2

Osteoporosis is a medical condition of global concern, with increasing incidence in both sexes. Bone mineral density (BMD), a highly heritable trait, has been proven a useful diagnostic factor in predicting fracture. Because medical information is lacking about male osteoporotic genetics, we conducted a genome-wide association study of BMD in Korean men. With 1,176 participants, we analyzed 4,414,664 single nucleotide polymorphisms (SNPs) after genomic imputation, and identified five SNPs and three loci correlated with bone density and strength. Multivariate linear regression models were applied to adjust for age and body mass index interference. Rs17124500 ($p=6.42{\times}10^{-7}$), rs34594869 ($p=6.53{\times}10^{-7}$) and rs17124504 ($p=6.53{\times}10^{-7}$) in 14q31.3 and rs140155614 ($p=8.64{\times}10^{-7}$) in 15q25.1 were significantly associated with lumbar spine BMD (LS-BMD), while rs111822233 ($p=6.35{\times}10^{-7}$) was linked with the femur total BMD (FT-BMD). Additionally, we analyzed the relationship between BMD and five genes previously identified in Korean men. Rs61382873 (p = 0.0009) in LRP5, rs9567003 (p = 0.0033) in TNFSF11 and rs9935828 (p = 0.0248) in FOXL1 were observed for LS-BMD. Furthermore, rs33997547 (p = 0.0057) in ZBTB and rs1664496 (p = 0.0012) in MEF2C were found to influence FT-BMD and rs61769193 (p = 0.0114) in ZBTB to influence femur neck BMD. We identified five SNPs and three genomic regions, associated with BMD. The significance of our results lies in the discovery of new loci, while also affirming a previously significant locus, as potential osteoporotic factors in the Korean male population.

임상연구 : 백내장적출술을 위한 안구후차단시 Remifentanil, Alfentanil, Fentanyl이 혈역학적 변화와 진통, 진정효과에 미치는 영향

임세근 ( Sei Keun Im ),구길회 ( Gill Hoi Koo ),강현 ( Hyun Kang ),백종화 ( Chong Wha Baek ),박정원 ( Jung Won Park ),정용훈 ( Yong Hun Jung ),우영철 ( Young Cheol Woo ),김진윤 ( Jin Yun Kim ),박선규 ( Sun Gyoo Park ) 대한마취과학회 2007 Korean Journal of Anesthesiology Vol.53 No.4

Background: This study was designed to compare the effects of remifentanil, alfentanil, and fentanyl on the hemodynamic changes, sedation, and analgesia when administered with small doses of midazolam in patients undergoing a retrobulbar block for cataract surgery. Methods: Sixty patients scheduled for cataract surgery were divided into 4 groups (n = 15 for each group). Firstly, group C received 5 ml of a normal saline solution, 3 min before a retrobulbar block. Next, group R received remifentanil 0.3μg/kg. Furthermore, group A received a 4.5μg/kg dose of alfentanil, 90 s before a retrobulbar block, and group F received fentanyl 0.6μg/kg, 210 s before a retrobulbar block. All solutions were mixed with normal saline to a 5 ml volume. In group R, A, and F, midazolam (0.5 mg for patients over the age of 65 years; 1.0 mg in patients under the age of 65 years) was injected 3 min before the retrobulbar block. Results: The systolic blood pressure in patients significantly increased at 1 or 2 minutes after a retrobulbar block in group C and at 1 minute in group F. For group R, the systolic blood pressure decreased significantly at 3, 4, 5, and 10 minutes, and at 2, 3, 4, 5, and 10 minute in group A. The mean OAA/S scale during a retrobulbar block significantly declined in groups R and A. The VAS score for pain was significantly lower in groups R and A, whereas the VAS anxiety index was significantly lower in groups R, A, F compared to group C (P<0.05). Conclusions: We found that the combination of remifentanil or alfentanil with midazolam showed better hemodynamic stability, sedative, and analgesic effects compared to fentanyl with midazolam in the retrobulbar block for cataract surgery. (Korean J Anesthesiol 2007; 53: 441~7)