• Genomics & Informatics
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• v.17 no.4
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• pp.48.1-48.6
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• 2019

Over the last decade, genome-wide association studies (GWASs) have provided an unprecedented amount of genetic variations that are associated with various phenotypes. However, previous GWAS were mostly conducted in European populations, and these biased results for non-Europeans may result in a significant reduction in risk prediction for non-Europeans. An issue with the early GWAS was the winner's curse problem, which led to misleading results when constructing the polygenic risk scores (PRS). Therefore, more non-European population-based studies are needed to validate reported variants and improve genetic risk assessment across diverse populations. In this study, we validated 422 variants independently associated with glycemic indexes, liver enzymes, and type 2 diabetes in 125,872 samples from a Korean population, and further validated the results by assessing publicly available summary statistics from European GWAS (n = 898,130). Among the 422 independently associated variants, 284, 320, and 361 variants were replicated in Koreans, Europeans, and either one of the two populations. In addition, the effect sizes for Koreans and Europeans were moderately correlated (r = 0.33-0.68). However, 61 variants were not replicated in both Koreans and Europeans. Our findings provide valuable information on effect sizes and statistical significance, which is essential to improve the assessment of disease risk using PRS analysis.

• Asian Oncology Nursing
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• v.10 no.1
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• pp.103-111
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• 2010

Purpose: This study was undertaken to establish the framework for development of the curriculum of genetics in Nursing Education. Methods: The Internet search, literature review of the US system of genetic nurses, genetic graduate nursing education programs and curricula for nurse in Korea were reviewed and analyzed. Results: American Nurses genetic system consists of APNG and the GCS and all the APNG credential provided by the GNCC of ISONG. The curriculums of genetic nursing education in the US are mainly conducted in of master's program and genetically related subjects consists of basic genetics subjects, basic applied genetics subjects, genetics in nursing subjects and practical training subjects. Lastly a genetic nursing education program in Korea 44 hr of lectures and practical training of 4 hr is composed of basic genetics, genetic cancer, genetics in nursing and practicum in the computer lab and online include family history assessment, pedigree construction, breast and colorectal cancer risk calculations, and ELSI discussions. Conclusion: This study suggested that genetic nursing education course needs in master's program as detailed subjects. Also the establishment of the genetic nurse system is an urgent needed.

• Genomics & Informatics
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• v.10 no.2
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• pp.99-105
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• 2012

Dyslipidemia, mainly characterized by high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, is an important etiological factor in the development of cardiovascular disease (CVD). Considering the relationship between childhood obesity and CVD risk, it would be worthwhile to evaluate whether previously identified lipid-related variants in adult subjects are associated with lipid variations in a childhood obesity study (n = 482). In an association analysis for 16 genome-wide association study (GWAS)-based candidate loci, we confirmed significant associations of a genetic predisposition to lipoprotein concentrations in a childhood obesity study. Having two loci (rs10503669 at LPL and rs16940212 at LIPC) that showed the strongest association with blood levels of TG and HDL-C, we calculated a genetic risk score (GRS), representing the sum of the risk alleles. It has been observed that increasing GRS is significantly associated with decreased HDL-C (effect size, $-1.13{\pm}0.07$) compared to single nucleotide polymorphism combinations without two risk variants. In addition, a positive correlation was observed between allelic dosage score and risk allele (rs10503669 at LPL) on high TG levels (effect size, $10.89{\pm}0.84$). These two loci yielded consistent associations in our previous meta-analysis. Taken together, our findings demonstrate that the genetic architecture of circulating lipid levels (TG and HDL-C) overlap to a large extent in childhood as well as in adulthood. Post-GWAS functional characterization of these variants is further required to elucidate their pathophysiological roles and biological mechanisms.

• BMB Reports
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• v.36 no.1
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• pp.1-11
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• 2003

The causative role of polycyclic aromatic hydrocarbons (PAH) in human carcinogenesis is undisputed. Measurements of PAH-DNA adduct levels in easily accessible white blood cells therefore represent useful early endpoints in exposure intervention of chemoprevention studies. The successful applicability of DNA adducts as early endpoints depends on several criteria:i.adduct levels in easily accessible surrogate tissues should reflect adduct levels in target-tissues, ii. toxicokinetics and the temporal relevance should be properly defined.iii. sources of inter- and intra-individual variability must be known and controllable, and finally iv. adduct analyses must have advantages as compared to other markers of PAH-exposure. In general, higher DNA adduct levels or a higher proportion of subjects with detectable DNA adduct levels were found in exposed individuals as compared with non-exposed subjects, but saturation may occur at high exposures. Furthermore, DNA adduct levels varied according to changes in exposure, for example smoking cessation resulted in lower DNA adduct levels and adduct levels paralleled seasonal variations of air-pollution. Intra-individual variation during continuous exposure was low over a short period of time (weeks), but varied significantly when longer time periods (months) were investigated. Inter-individual variation is currently only partly explained by genetic polymorphisms in genes involved in PAH-metabolism and deserves further investigation. DNA adduct measurement may have three advantages over traditional exposure assessment: i. they can smooth the extreme variability in exposure which is typical for environmental toxicants and may integrate exposure over a longer period of time. Therefore, DNA adduct assessment may reduce the monitoring effort. ii. Biological monitoring of DNA adducts accounts for all exposure routes. iii. DNA adducts may account for inter-individual differences in uptake, elimination, distribution, metabolism and repair amongst exposed individuals. In conclusion, there is now a sufficiently large scientific basis to justify the application of DNA adduct measurement as biomarkers in exposure assessment and intervention studies. Their use in risk-assessment, however, requires further investigation.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.3001-3006
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• 2016

Background: The cancer progression of oral leukoplakia is an important watchpoint in the follow-up observation of the patients. However, potential malignancies of oral leukoplakia cannot be estimated by histopathologic assessment alone. We evaluated genetic abnormalities at the level of copy number variation (CNV) to investigate the risk for developing cancer in oral leukoplakias. Materials and Methods: The current study used 27 oral leukoplakias with histological evidence of dysplasia. The first group (progressing dysplasia) consisted of 7 oral lesions from patients with later progression to cancer at the same site. The other group (non-progressing dysplasia) consisted of 20 lesions from patients with no occurrence of oral cancer and longitudinal follow up (>7 years). We extracted DNA from Formalin-Fixed Paraffin-Embedded (FFPE) samples and examined chromosomal loci and frequencies of CNVs using Taqman copy number assays. Results: CNV frequently occurred at 3p, 9p, and 13q loci in progressing dysplasia. Our results also indicate that CNV at multiple loci-in contrast to single locus occurrences-is characteristic of progressing dysplasia. Conclusions: This study suggests that genetic abnormalities of the true precancer demonstrate the progression risk which cannot be delineated by current histopathologic diagnosis.

• Nuclear Engineering and Technology
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• v.56 no.2
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• pp.644-654
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• 2024

After the Tohoku earthquake and tsunami (Japan, 2011), regulatory efforts to mitigate external hazards have increased both the safety requirements and the total capital cost of nuclear power plants (NPPs). In these circumstances, identifying not only disaster robustness but also cost-effective capacity setting of NPPs has become one of the most important tasks for the nuclear power industry. A few studies have been performed to relocate the seismic capacity of NPPs, yet the effects of multiple hazards have not been accounted for in NPP capacity optimization. The major challenges in extending this problem to the multihazard dimension are (1) the high computational costs for both multihazard risk quantification and system-level optimization and (2) the lack of capital cost databases of NPPs. To resolve these issues, this paper proposes an effective method that identifies the optimal multihazard capacity of NPPs using a multi-objective genetic algorithm and the two-stage direct quantification of fault trees using Monte Carlo simulation method, called the two-stage DQFM. Also, a capacity-based indirect capital cost measure is proposed. Such a proposed method enables NPP to achieve safety and cost-effectiveness against multi-hazard simultaneously within the computationally efficient platform. The proposed multihazard capacity optimization framework is demonstrated and tested with an earthquake-tsunami example.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2004.11a
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• pp.271-274
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• 2004

Nutritional genomics is a new field of study of how nutrition interacts with an individual's genome or individual responds to individual diets. Systematic approach of nutritional genomics will likely provide important clues about responders and non-responders. The current interest in personalizing health stems from the breakthroughs emerging in integrative technologies of genomics and epigenomics and the identification of genetic and epigentic diversity in individual's genetic make-up that are associated with variations in many aspects of health, including diet-related diseases. Microarray is a powerful screen system that is being also currently employed in nutritional research. Monitoring of gene expression at genome level is now possible with this technology, which allows the simultaneous assessment of the transcription of tens of thousands of genes and of their relative expression of pathological cells such tumor cells compared with that of normal cells. Epigenetic events such as DNA methylation can result in change of gene expression without involving changes in gene sequence. Recent developed technology of DNAarray-based methylation assay will facilitate wide study of epigenetic process in nutrigenomics. Some of the areas that would benefitfrom these technologies include identifying molecular targets (Biomarkers) for the risk and benefit assessment. These characterized biomarkers can reflect expose, response, and susceptibility to foods and their components. Furthermore the identified new biomarker perhaps can be utilized as a indicator of delivery system fur optimizing health.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3973-3980
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• 2014

Prostate adenocarcinoma is one of the leading causes of cancer related mortality in men but still limited knowledge is available about its associated functional SNPs including rs1042522 (Pro72Arg). The present study was undertaken to explore the association of this SNP with susceptibility to prostate adenocarcinoma along with its structural and functional impacts in the Pakistani population in a case-control study. Three-dimensional structure of human TP53 with Pro72Arg polymorphism was predicted through homology modeling, refined and validated for detailed structure-based assessment. We also carried out a HuGE review of the previous available data for this polymorphism. Different genetic models were used to evaluate the genotypes association with the increased risk of PCa (Allelic contrast: OR=0.0.34, 95%CI 0.24-0.50, p=0.000; GG vs CC: OR=0.17, 95%CI 0.08-0.38, p=0.000; Homozygous: OR=0.08, 95%CI 0.04-0.15, p=0.000; GC vs CC: OR=2.14, 95%CI 1.01-4.51, p=0.046; Recessive model: OR=0.10, 95%CI 0.05-0.18, p=0.000; Log Additive: OR=3.54, 95%CI 2.13-5.89, p=0.000) except the Dominant model (OR=0.77, 95%CI 0.39-1.52, p=0.46). Structure and functional analysis revealed that the SNP in the proline rich domain is responsible for interaction with HRMT1L2 and WWOX. In conclusion, it was observed that the Arg coding G allele is highly associated with increased risk of prostate adenocarcinoma in the Pakistani population (p=0.000).

• Proceedings of the Korea Society of Environmental Biology Conference
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• 2004.05a
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• pp.1-15
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• 2004

Higher plants can be valuable genetic assay systems for monitoring environmental pollutants and evaluating their biological toxicity. Two assays are considered ideal for in situ monitoring and testing of soil, airborne and aqueous mutagenic agents; the Tradescantia stamen hair assay for somatic cell mutations and the Tradescantia micronucleus assay for chromosome aberrations. Both assays can be used for in vivo and in vitro testing of mutagens. Since higher plant systems are now recognized as excellent indicators and have unique advantages over in situ monitoring and screening, higher plant systems could be accepted by regulatory authorities as an alternative first-tier assay system for the detection of possible genetic damages resulting from the pollutants or chemicals used and produced by industrial sectors. It has been concluded that potential mutagen and carcinogen such as the heavy metals among indoor air particulates, volatile compounds in the working places, soil, and water pollutants contribute to the overall health risk. This contribution can be considerable under certain circumstances. It is therefore important to identify the level of genotoxic activity in the environment and to relate it to the biomarkers of a health risk in humans. The results from the higher plant bioassays could make a significant contribution to assessing the risks of pollutants and protecting the public firom agents that can cause mutation anuor cancer. The plant bioassays, which are relatively inexpensive and easy to handle, are recommended for the scientists who are interested in monitoring pollutants and evaluating their environmental toxicity to living organisms.

• Journal of Interdisciplinary Genomics
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• v.3 no.1
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• pp.7-12
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• 2021

Adverse drug reactions (ADRs) is a hypersensitivity reactions to specific medications, and remain a common and major problem in healthcare. ADRs suchc as drug-induced liver injury and life-threatening severe cutaneous adverse drug reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms can be occurred by uncontrolled expansion of oligoclonal T cells according to genetically predisposing HLA. In this review, I summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.