• Korean Journal of Clinical Pharmacy
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• v.24 no.4
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• pp.231-239
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• 2014

Background and objective: Pravastatin has been shown to have favorable risk-benefit profile when it is administered to hypercholesterolemic subjects to prevent cardiovascular events. However, subjects with impaired OATP1B1 activity may be more susceptible to pravastatin-induced muscle toxicity than subjects with normal OATP1B1 activity. A systematic review was conducted to evaluate the effect of SLCO1B1 genetic polymorphism on pharmacokinetics of pravastatin. Method: Medline$^{(R)}$ and Embase$^{(R)}$ were searched for relevant studies until July 2013. The search terms used were pravastatin AND (SLCO1B1 OR OATP1B1 OR LST1 OR SLC21A6) AND (gene OR $genetic^*$ OR $genomic^*$ OR $pharmacogenet^*$ OR $pharmacogenom^*$ OR $polymorph^*$). Results: A meta-analysis of the area under the concentration-time curve (AUC) of pravastatin in $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ was conducted. Five studies met all the inclusion criteria and methodological requirements. There was no statistically significant difference in the AUC value between $SLCO1B1^*15$ and $SLCO1B1^*1a/^*1a$ (p=0.728). However, $SLCO1B1^*15$ participants exhibited significantly higher AUC values than $SLCO1B1^*1b/^*1b$ carriers (p<0.001). In case of $SLCO1B1^*15^*15$ carriers, they had significantly higher AUC value than $SLCO1B1^*1a/^*1a$ subjects (p=0.002). Lastly, compared with to the subjects of $SLCO1B1^*1a/^*1a$, the carriers of heterozygous $SLCO1B1^*15$ increased the AUC value of pravastatin statistically significantly in Asian population (p=0.014). Conclusion: The present meta-analysis suggests that subjects with $SLCO1B1^*15$ are associated with increased AUC of pravastatin.

• Journal of Embryo Transfer
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• v.32 no.3
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• pp.165-170
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• 2017

Pigs have been extensively used as mediators of xenotransplantation research. Specifically, the Massachusetts General Hospital (MGH) miniature pig was developed to fix major histocompatibility antigens for use in xenotransplantation studies. We generated transgenic pigs for xenotransplantation using MGH pigs. However, it has not been studied yet whether these pigs show similarity of reproductive physiological characteristics to wild types of MGH miniature pig. In this study we analyzed the estrous cycles and pregnancy characteristics of wild type (WT) and transgenic MGH miniature pigs, which were ${\alpha}1,3$-galactosyltransferase (GalT) heterozygous and homozygous knock-out, and membrane cofactor protein (MCP) inserted in its locus, $GalT^{-MCP/+}$ and $GalT^{-MCP/-MCP}$ pigs. Estrous cycles of WT, $GalT^{-MCP/+}$ and $GalT^{-MCP/-MCP}$ pigs were $20.9{\pm}0.74$, $20.1{\pm}1.26$, and $17.3{\pm}0.87days$, respectively, and periods of estrous were $3.2{\pm}0.10$, $3.1{\pm}0.12$, and $3.1{\pm}0.11days$. The periods of gestation of WT, $GalT^{-MCP/+}$ and $GalT^{-MCP/-MCP}$ pigs were $114.2{\pm}0.37$, $113.3{\pm}0.67$, and $115.4{\pm}0.51days$, respectively. Litter sizes of WT, $GalT^{-MCP/+}$ and $GalT^{-MCP/-MCP}$ pigs were $4.8{\pm}0.35$, $4.8{\pm}1.11$ and $3.0{\pm}0.32$ respectively. There were no significant differences on estrous cycle, periods of estrous and gestation, and litter size among WT, $GalT^{-MCP/+}$ and $GalT^{-MCP/-MCP}$ pigs, meaning that GalT knock-out and additional expression MCP of the MGH miniature pig did not effect on reproduction traits. These results provide relevant information to establish breeding system for MGH transgenic pig, and for propagation of $GalT^{-MCP/-MCP}$ pig to supply for xenotransplantation research.

• Journal of Embryo Transfer
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• v.32 no.3
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• pp.73-79
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• 2017

Transplantation is considered to be a very useful approach to improve human welfare and to prolong life-span. Heterologous organ transplantation using pig organs which are similar to human beings and easy to make mass-production has known as one of the alternatives. To ensure potential usage of the pig organ for transplantation application, it is essentially required to generate transgenic pig modifying immuno-related genes. Previously, we reported production of heterozygous ${\alpha}1,3$-galactosyltransferase (GalT) knock-out and human membrane cofactor protein (MCP) expressing pig ($GalT^{-MCP/+}$), which is enforced for suppression of hyperacute and acute immunological rejection. In this study, we reported generation of homozygous pig ($GalT^{-MCP/-MCP}$) by crossbreeding $GalT^{-MCP/+}$ pigs. Two female founders gave birth to six of $GalT^{-MCP/-MCP}$, and seven $GalT^{-MCP/+}$ pigs. We performed quantitative real-time PCR, western blot, and flow cytometry analyses to confirm GalT and MCP expression. We showed that fibroblasts of the $GalT^{-MCP/-MCP}$ pig do not express GalT and its product Gal antigen, while efficiently express MCP. We also showed no expression of GalT, otherwise expression of MCP at heart, kidney, liver and pancreas of transgenic pig. Taken together, we suggest that the $GalT^{-MCP/-MCP}$ pig is a useful candidate to apply xenotransplantation study.

• Journal of Animal Science and Technology
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• v.52 no.6
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• pp.475-480
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• 2010

The bovine fatty acid binding protein 4 (FABP4) plays an important role to uptake intracellular fatty acid. It has been previously reported as a positional candidate gene for marbling score in livestock. The re-sequencing of FABP4 gene detected a polymorphic AT repeated sequence in intron II of FABP4 gene. Allelic distribution for this microsatellite marker was examined in other cattle breeds. A total of 8 alleles were detected with diverse repeat units (14 to 21 AT repeat) in Hanwoo and 7 breeds. Of the 8 alleles, the predominant alleles were $[AT]_{16}$, $[AT]_{18}$ and $[AT]_{19}$ in the Hanwoo and 7 cattle breeds. The linear mixed model for genotypic effect (3237AT) on carcass traits showed a significant effect on marbling score (MAR P=0.025) and live weight (LWT; P=0.04) in the 583 Hanwoo cattle population. Live weight (LW) was highest in the homozygous $(AT)_{17}$ genotype ($557.5{\pm}6.94$) and lowest in the heterozygous $(AT)_{16/17}$ genotype ($521.7{\pm}7.70$). On the other hand, the homozygous $(AT)_{17}$ genotype ($3.0{\pm}0.15$) has the highest effect on marbling score and the lowest effect was in homozygous (AT)$_{18}$ genotype ($2.2{\pm}0.15$). The marbling score difference between both groups was 0.8 which is around two times higher than SNP genotype effect on marbling score in Limousin $\times$ Wagyu crosses.

• Radiation Oncology Journal
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• v.36 no.3
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• pp.218-226
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• 2018

Purpose: Standard treatment for locally advanced rectal cancer consists of neoadjuvant radiochemotherapy with concomitant fluoropyrimidine or oxaliplatin and surgery with curative intent. Pathological complete response has shown to be predictive for better outcome and survival; nevertheless there are no biological or genetic factors predictive for response to treatment. We explored the correlation between the single nucleotide polymorphisms (SNPs) GSTP1 (A313G) and XRCC1 (G28152A), and the pathological complete response and survival after neoadjuvant radiochemotherapy in locally advanced rectal cancer patients. Materials and Methods: Genotypes GSTP1 (A313G) and XRCC1 (G28152A) were determined by pyrosequencing technology in 80 patients affected by locally advanced rectal cancer. Results: The overall rate of pathological complete response in our study population was 18.75%. Patients homozygous AA for GSTP1 (A313G) presented a rate of pathological complete response of 26.6% as compared to 8.5% of the AG+GG population (p = 0.04). The heterozygous comparison (AA vs. AG) showed a significant difference in the rate of pathological complete response (26.6% vs. 6.8%; p = 0.034). GSTP1 AA+AG patients presented a 5- and 8-year cancer-specific survival longer than GSTP1 GG patients (87.7% and 83.3% vs. 44.4% and 44.4%, respectively) (p = 0.014). Overall survival showed only a trend toward significance in favor of the haplotypes GSTP1 AA+AG. No significant correlations were found for XRCC1 (G28152A). Conclusion: Our results suggest that GSTP1 (A313G) may predict a higher rate of pathological complete response after neoadjuvant radiochemotherapy and a better outcome, and should be considered in a more extensive analysis with the aim of personalization of radiation treatment.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.18 no.1
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• pp.48-54
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• 2015

Purpose: Metabolic liver disease (MLD) often progresses to life-threatening conditions. This study intends to describe the outcomes of liver transplantation (LTx) for MLD at a living donor-dominant transplantation center where potentially heterozygous carrier grafts are employed. Methods: We retrospectively evaluated the medical records of 54 patients with MLD who underwent LTx between November 1995 and February 2012 at Asan Medical Center in Seoul, Korea. The cumulative graft and patient survival rates were analyzed according to patient age, and living or deceased donor LTx. Recurrence of the original disease was also investigated. Results: The post-transplant cumulative patient survival rates at one, five, and 10 years were 90.7%, 87.5% and 87.5%, and the graft survival rates were 88.8%, 85.5%, and 85.5%, respectively. There were no differences in the patient survival rates according to the recipient age, human leukocyte antigen matching, and living or deceased donor LTx. There were also no differences in the patient survival rates between the MLD and the non-MLD groups for children. Recurrence of the original metabolic disease was not observed in any patient during the follow-up period. Conclusion: Our results suggest that the living donor-dominant transplantation program is well-tolerated in MLD without recurrence of the original MLD using all types of transplantation.

• Journal of Life Science
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• v.21 no.2
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• pp.194-201
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• 2011

Caudal-related homeodomain proteins play critical roles in intestine development and maintenance from Drosophila to humans. The loss or reduction of CDX1 and CDX2 are known to be associated with colon cancers. It has been well known that colorectal carcinogenesis is associated with serious oxidative stress and that catalase is decreased in colon carcinomas. However, the underlying molecular mechanisms remain elusive. Here, we report that Caudal-related homeodomain proteins positively regulate catalase expression in both Drosophila and humans. We found that Drosophila caudal heterozygotes have a decreased catalase expression and increased ROS generation in the hindgut, and that the overexpression of Caudal increases catalase promoter activity and catalase mRNA levels. We also found that CDX1 and CDX2 up-regulate catalase promoter activity and protein levels in HCT116 cells - human colorectal carcinoma cell lines. The level of catalase protein in several colorectal carcinoma cell lines was associated with CDX1 expression. These results suggest that CDX1 and CDX2 may be involved in intestinal homeostasis and tumorigenesis via regulation of catalase expression.

• Journal of the Korean Child Neurology Society
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• v.25 no.3
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• pp.200-203
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• 2017

Spinocerebellar ataxias (SCAs) are autosomal dominant neurodegenerative disorders which disrupt the afferent and efferent pathways of the cerebellum that cause cerebellar ataxia. Spectrin beta non-erythrocytic 2 (SPTBN2) gene encodes the ${\beta}-III$ spectrin protein with high expression in Purkinje cells that is involved in excitatory glutamate signaling through stabilization of the glutamate transporter, and its mutation is known to cause spinocerebellar ataxia type 5. Three years and 5 months old boy with delayed development showed leukodystrophy and cerebellar atrophy in brain magnetic resonance imaging (MRI). Diagnostic exome sequencing revealed that the patient has heterozygous mutation in SPTBN2 (p.Glu1251Gln) which is a causative genetic mutation for spinocerebellar ataxia type 5. With the patient's clinical findings, it seems reasonable to conclude that p.Glu1251Gln mutation of SPTBN2 gene caused spinocerebellar ataxia type 5 in this patient.

• FLOWER RESEARCH JOURNAL
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• v.18 no.3
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• pp.193-200
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• 2010

Current rose cultivars are all composed of heterozygous genome due to long history of out crossing including interspecific hybridization. It has been adapted by artificial selection and crossing by breeders that mainly based on the crossing with fertile pollen derived from inter- or intra-specific hybridization. Pollen viability and germination ability tests provide valuable information for the designing of parentage for more successful breeding efficacy. In this study, we tested the pollen viability and germination ability in seven rose cultivars to find any relationship among several factors including pollen size, ploidy levels, and crossing compatibility. The pollen viability showed wide ranges from 39% 'Pinocchio' as minimum to 82% 'Scarlet Mimi' as maximum, whereas pollen germination rate were from 1% 'Mini Rosa' to 41% 'Scarlet Mimi' as a highest. Pollen size ranged from 41.3 to $45.4{\mu}m$ in large sized pollen and 30.7 to $37.4{\mu}m$ in small sized pollen. The mean diameter of large sized pollen is approximately 10-40% bigger than that of small sized pollen. There are positive relationships among ploidy level, total chromosome length, and pollen size. Crossing list showed that seed setting ratio and seed germination were related to pollen viability, pollen germination, and ploidy level.

• Korean Journal of Breeding Science
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• v.40 no.4
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• pp.414-421
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• 2008

We conducted a QTL analysis of agronomic traits using 117 $BC_3F_5$ and $BC_3F_6$ lines developed from a cross between Ilpumbyeo and Moroberekan. Genotypes of 117 $BC_3F_5$ lines were determined using 134 simple sequence repeat (SSR) markers. A total of 832 Moroberekan chromosome segments with 410 homozygous and 422 heterozygous, respectively, were detected, and the genetic distance of introgression segments ranged from 0.5 cm to 112.1 cm. A linkage map constructed using 134 SSR markers was employed to characterize quantitative trait loci (QTL). The 117 $BC_3F_5$ and $BC_3F_6$ lines were evaluated for seven agronomic traits at two locations in 2006 and 2007 and at one location in 2007. A total of 26 QTLs were identified for seven traits including days to heading, and the phenotypic variance explained by each QTL ranged from 9.2% to 24.2%. Moroberekan alleles contributed positive effects in the Ilpumbyeo background at eleven QTL loci including panicle length and spikelets per panicle. Five QTLs, two for days to heading and one each for culm length, panicle length and spikelets per panicle were consistently detected in every occasions indicating that these QTLs are stable. Among them, two QTLs, spp6 for spikelets per panicle and pl6 for paniclel length were localized in the similar region. Increase in spikelets per panicle at this locus might be due to the increase in panicle length, because both traits were associated with increase in spikelets per panicle and panicle length due to the presence of the Moroberekan allele. These Moroberekan QTLs might be useful in breeding programs to develop high-yielding cultivars.