• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.479-484
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• 2013

Given the CYP3A4 and CYP3A5's impact on the efficacy of drugs, the genetic backgrounds of individuals and populations are regarded as an important factor to be considered in the prescription of personalized medicine. However, genetic studies with Korean population are relatively scarce compared to those with other populations. In this study, we aimed to identify CYP3A4/5 polymorphisms and compare the genotype distributions among five ethnicities. To identify CYP3A4/5 SNPs, we first performed direct sequencing with 288 DNA samples which consisted of 96 Koreans, 48 European-Americans, 48 African-Americans, 48 Han Chinese, and 48 Japanese. The direct sequencing identified 15 novel SNPs, as well as 42 known polymorphisms. We defined the genotype distributions, and compared the allele frequencies among five ethnicities. The results showed that minor allele frequencies of Korean population were similar with those of the Japanese and Han Chinese populations, whereas there were distinct differences from European-Americans or African-Americans. Among the pharmacogenetic markers, frequencies of $CYP3A4^*1B$ (rs2740574) and $CYP3A5^*3C$ (rs776742) in Asian groups were different from those in other populations. In addition, minor allele frequency of $CYP3A4^*18$ (rs28371759) was the highest in Korean population. Additional in silico analysis predicted that two novel non-synonymous SNPs in CYP3A5 (+27256C>T, P389S and +31546T>G, I488S) could alter protein structure. The frequency distributions of the identified polymorphisms in the present study may contribute to the expansion of pharmacogenetic knowledge.

• 대한약리학회:학술대회논문집
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• 2006.11a
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• pp.70-70
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• 2006

• Animal Bioscience
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• v.34 no.11
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• pp.1757-1765
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• 2021

Objective: The swine leukocyte antigen (SLA) gene group, which is closely linked and highly polymorphic, has important biomedical significance in the protection and utilization of germplasm resources. However, genetic polymorphism analyses of SLA microsatellite markers in Chinese miniature pigs are limited. Methods: Eighteen pairs of microsatellite primers were used to amplify the SLA regions of seven miniature pig breeds and three wild boar breeds (n = 346) from different regions of China. The indexes of genetic polymorphism, including expected heterozygosity (He), polymorphic information content (PIC), and haplotype, were analyzed. The genetic differentiation coefficient (Fst) and neighbor-joining methods were used for cluster analysis of the breeds. Results: In miniature pigs, the SLA I region had the highest numbers of polymorphisms, followed by the SLA II and SLA III regions; the region near the centromere had the lowest number of polymorphisms. Among the seven miniature pig breeds, Diannan small-ear pigs had the highest genetic diversity (PIC value = 0.6396), whereas the genetic diversity of the Hebao pig was the lowest (PIC value = 0.4330). The Fst values in the Mingguang small-ear, Diannan small-ear, and Yunnan wild boars were less than 0.05. According to phylogenetic cluster analysis, the South-China-type miniature pigs clustered into one group, among which Mingguang small-ear pigs clustered with Diannan small-ear pigs. Haplotype analysis revealed that the SLA I, II, and III regions could be constructed into 13, 7, and 11 common haplotypes, respectively. Conclusion: This study validates the high genetic diversity of the Chinese miniature pig. Mingguang small-ear pigs have close kinship with Diannan small-ear pigs, implying that they may have similar genetic backgrounds and originate from the same population. This study also provides a foundation for genetic breeding, genetic resource protection, and classification of Chinese miniature pigs.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.12
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• pp.1637-1643
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• 2011

Korean native chickens are a very valuable chicken population in Korea and their prices are higher than that of commercial broilers. In order to discriminate two commercial Korean native chicken populations (CCP1 and CCP2), single nucleotide polymorphisms (SNPs) from mitochondrial (mt) DNA D-loop sequences and LEI0258 marker polymorphisms in the major histocompatibility complex (MHC) region were investigated. A total of 718 birds from nine populations were sampled and 432 mtDNA sequences were obtained. Of these, two commercial Korean native chicken populations (363 birds) were used for investigation of their genetic relationship and breed differentiation. The sequence data classified the chickens into 20 clades, with the largest number of birds represented in clade 1. Analysis of the clade distribution indicated the genetic diversity and relation among the populations. Based on the mtDNA sequence analysis, three selected SNPs from mtDNA polymorphisms were used for the breed identification. The combination of identification probability (Pi) between CCP1 and CCP2 using SNPs from mtDNA and LEI0258 marker polymorphisms was 86.9% and 86.1%, respectively, indicating the utility of these markers for breed identification. The results will be applicable in designing breeding and conservation strategies for the Korean native chicken populations and also used for the development of breed identification markers.

• 대한예방의학회:학술대회논문집
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• 1999.10a
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• pp.1-15
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• 1999

In a case-control study to evaluate the factors involved in the development of hepatocellular carcinoma, polymorphisms of the p53 gene were compared in 68 cases mostly infected with hepatitis C virus (HCV) and 68 controls matched for sex and age: DNA from peripheral blood leukocytes was analyzed by the polymerase chain reaction-single strand conformation polymorphism method and direct sequencing. Polymorphisms analyzed were those in exon 4 (CCC vs. CGC, Pro vs. Arg at codon 72, Al allele vs. A2 allele), intron 2 (C vs. G at nucleotide 38, Al vs. A2), intron 3 (C vs. A at nucleotide 65, Al vs. A2; absence and presence of 16 base pair repeat at nucleotides 24 to 39, Al vs. A2), intron 6 (A vs. G at nucleotide 62, Al vs. A2) and intron 7 (C and T vs. T and G at nucleotides 72 and 92, Al vs. A2). A significantly higher frequency of the allele for CCC (Pro, Al) at codon 72 of exon 4 was found in cases (39%) than in controls (26%) (p<0.05). Highly significant linkage of the polymorphisms in exon 4, intron 2, intron 3 and intron 7, and between the intron 3-16 bp duplication and polymorphism in intron 6 also was found. Matched Fair analysis showed significantly higher frequencies of certain haplotypes (1-1-1-1-2-2 or 1-1-2-1-2-1 for exon 4, intron 2, intron 3, the intron 3-16 bp duplication, intron 6 and intron 7) in cases than in controls (p=0.014, OR=2.27, 95% CI= 1.08-5.12). No preference of specific p53 polymorphisms for specific HCV genotype was detected. These findings suggest that in hepatocarcinogenesis mainly due to HCV infection, genetic factors may be involved and that genetic markers can serve as predictors of a high-risk group for hepatocarcinogenesis.

• Korean Journal of Biological Psychiatry
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• v.26 no.2
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• pp.88-93
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• 2019

Objectives Psychological stress has been known to increase the risk of schizophrenia. Because stress responses are mainly mediated by cortisol, the action of the glucocorticoid receptors (Nuclear Receptor Subfamily 3 Group C Member 1, NR3C1) is possibly related to the pathogenesis of schizophrenia. In this study, we investigated the associations between polymorphisms of NR3C1 and schizophrenia. Methods Four single nucleotide polymorphisms (SNPs) (rs17100236, rs2963155, rs9324924, and rs7701443) of NR3C1 were genotyped in 208 patients with schizophrenia and 339 healthy individuals. A chi-square test was performed to test differences in allele distributions among groups. A multiple logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and multiple inheritance models to analyze the associations between schizophrenia and SNPs (the dominant, recessive and additive models). Results The minor allele frequencies of two SNPs were significantly higher in the schizophrenia group than in those of the control group (rs2963155 G > A : 0.25 vs. 0.18, p = 0.0066 ; rs7701443 A > G : 0.40 vs. 0.33, p = 0.012). The genotype frequencies of two SNPs were found to be significantly different between patients with schizophrenia and controls in the dominant model (rs2963155 : AG/GG vs. AA, OR = 1.66, 95% CI = 1.16-2.38, p = 0.0055, rs7701443 : AG/AA vs. GG, OR = 1.61, 95% CI = 1.11-2.34, p = 0.01) and the log-additive model (rs2963155 : AG vs. GG vs. AA, OR = 1.54, 95% CI = 1.13-2.10, p = 0.0067). Conclusions This study showed significant associations between NR3C1 polymorphisms and schizophrenia. It suggests that NR3C1 may play a role in the pathogenesis of schizophrenia.

• Genomics & Informatics
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• v.7 no.4
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• pp.195-202
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• 2009

BIRC5 (Survivin) belongs to the inhibitor of apoptosis gene family. The BIRC5 protein inhibits caspases and consequently blocks apoptosis. Thus, BIRC5 contributes to the progression of cancer allowing for continued cell proliferation and survival. In this study, we identified eight sequence variants of BIRC5 through direct DNA sequencing. Among the eight single nucleotide polymorphisms (SNPs), six common variants with frequencies higher than 0.05 were selected for larger-scale genotyping (n=1,066). Results of the study did not show any association between the promoter region polymorphisms and the clearance of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence. This is in line with a previous study in which polymorphisms in the promoter region does not influence the function of BIRC5. Initially, we were able to detect a signal with the ＋9194A>G, which disappeared after multiple corrections but led to a change in amino acid. Similarly, we were also able to detect an association signal between two haplotypes (haplotype-2 and haplotype-5) on the onset age of HCC and/or HCC occurrence, but the signals also disappeared after multiple corrections. As a result, we concluded that there was no association between BIRC5 polymorphisms and the clearance HBV infection and/or HCC occurrence. However, our results might useful to future studies.

• Genomics & Informatics
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• v.11 no.4
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• pp.254-262
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• 2013

The multidrug resistance protein 2 (MRP2, ABCC2) gene may determine individual susceptibility to adverse drug reactions (ADRs) in the central nervous system (CNS) by limiting brain access of antiepileptic drugs, especially valproic acid (VPA). Our objective was to investigate the effect of ABCC2 polymorphisms on ADRs caused by VPA in Korean epileptic patients. We examined the association of ABCC2 single-nucleotide polymorphisms and haplotype frequencies with VPA related to adverse reactions. In addition, the association of the polymorphisms with the risk of VPA related to adverse reactions was estimated by logistic regression analysis. A total of 41 (24.4%) patients had shown VPA-related adverse reactions in CNS, and the most frequent symptom was tremor (78.0%). The patients with CNS ADRs were more likely to have the G allele (79.3% vs. 62.7%, p=0.0057) and the GG genotype (61.0% vs. 39.7%, p=0.019) at the g.-1774delG locus. The frequency of the haplotype containing g.-1774Gdel was significantly lower in the patients with CNS ADRs than without CNS ADRs (15.8% vs. 32.3%, p=0.0039). Lastly, in the multivariate logistic regression analysis, the presence of the GG genotype at the g.-1774delG locus was identified as a stronger risk factor for VPA related to ADRs (odds ratio, 8.53; 95% confidence interval, 1.04 to 70.17). We demonstrated that ABCC2 polymorphisms may influence VPA-related ADRs. The results above suggest the possible usefulness of ABCC2 gene polymorphisms as a marker for predicting response to VPA-related ADRs.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.3
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• pp.306-315
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• 2021

Purpose: Obesity is defined as the abnormal or excessive accumulation of fat over acceptable limits. Leptin is a metabolic hormone present in the circulation in amounts proportional to fat mass. Leptin reduces food intake and increases energy expenditure, thus regulating body weight and homeostasis. Various polymorphisms are present in the leptin gene and its receptor. These polymorphisms may be associated with obesity. This study aimed to show the association of leptin (+19) AG, leptin (2548) GA, and Gln223Arg leptin receptor polymorphisms with obesity and metabolic syndrome in Turkish children aged 6-17 years, and to conduct further investigations regarding the genetic etiology of obesity. Methods: A total of 174 patients diagnosed with obesity and 150 healthy children who were treated at Tokat Gaziosmanpasa Medical School Hospital between September 2014 and March 2015 were included in this study. The ages of the children were between 6 and 17 years, and anthropometric and laboratory results were recorded. Genotyping of leptin (+19) AG, leptin (2548) GA, and leptin receptor Gln223Arg polymorphisms was performed by polymerase chain reaction. Results: An association between leptin receptor Gln223Arg gene polymorphism and obesity was detected. Conclusion: Further studies are needed to determine the role of genetic etiologies and to indicate the role of leptin signal transmission impairment in the pathogenesis of obesity. We hope that gene therapy can soon provide a solution for obesity.

• Biomedical Science Letters
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• v.18 no.2
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• pp.87-95
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• 2012

Hypertension is a complex disease that results from the interaction of genetic and environmental influences and heritability is influenced by about one-third to one-half. However, the specific genetic variants determining risk for hypertension are still largely unknown. Here, we performed association analysis to elucidate the possible relations of genetic polymorphisms in ESR1 gene with blood pressure traits. By examining genotype data of a total of 3,804 women in the Korean Association REsource (KARE) study, we discovered the ESR1 gene polymorphisms are associated with blood pressure and hypertension. The highest significant polymorphisms were rs2982571 (${\beta}=-1.56$, $P=6.8{\times}10^{-3}$) with systolic blood pressure (SBP), rs9322335 (${\beta}=-0.61$, P=0.013) with diastolic blood pressure (DBP), and rs851985 (OR=0.78, CI: 0.65~0.94, $P=8.6{\times}10^{-3}$) with hypertension. In the 5 SNPs (rs2982571, rs851985, rs851983, rs851981, and rs851980), their ${\beta}$-values in SBP and/or DBP showed consistent trends with the odds ratios (ORs) of hypertension, and these 5 SNPs were composed with one LD block. Consequently, we found statistically significant SNPs in ESR1 gene that are associated with both blood pressure and hypertension traits. These results suggested that the individuals with the minor alleles of the 5 SNPs in the ESR1 gene may be less susceptible to the development of hypertension in the Korean women.