• Journal of Preventive Medicine and Public Health
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• 제49권5호
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• pp.253-259
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• 2016

Objectives: Central obesity plays a major role in the development of many chronic diseases, including cardiovascular disease and cancer. Chronic stress may be involved in the pathophysiology of central obesity. Although several large-scale genome-wide association studies have reported susceptibility genes for central adiposity, the effects of interactions between genes and psychosocial stress on central adiposity have rarely been examined. A recent study focusing on Caucasians discovered the novel gene early B-cell factor 1 (EBF1), which was associated with central obesity-related traits via interactions with stress levels. We aimed to evaluate EBF1 gene-by-stress interaction effects on central adiposity traits, including visceral adipose tissue (VAT), in Korean adults. Methods: A total of 1467 Korean adults were included in this study. We selected 22 single-nucleotide polymorphisms (SNPs) in the EBF1 gene and analyzed their interactions with stress on central adiposity using additive, dominant, and recessive genetic modeling. Results: The four SNPs that had strong linkage disequilibrium relationships (rs10061900, rs10070743, rs4704967, and rs10056564) demonstrated significant interactions with the waist-hip ratio in the dominant model ($p_{int}$<0.007). In addition, two other SNPs (rs6556377 and rs13180086) were associated with VAT by interactions with stress levels, especially in the recessive genetic model ($p_{int}$<0.007). As stress levels increased, the mean values of central adiposity traits according to SNP genotypes exhibited gradual but significant changes (p<0.05). Conclusions: These results suggest that the common genetic variants for EBF1 are associated with central adiposity through interactions with stress levels, emphasizing the importance of managing stress in the prevention of central obesity.

• Radiation Oncology Journal
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• 제33권2호
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• pp.149-154
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• 2015

Purpose: We performed exome sequencing in a breast cancer family without BRCA mutations. Materials and Methods: A family that three sisters have a history of breast cancer was selected for analysis. There were no family members with breast cancer in the previous generation. Genetic testing for BRCA mutation was negative, even by the multiplex ligation-dependent probe amplification method. Two sisters with breast cancer were selected as affected members, while the mother of the sisters was a non-affected member. Whole exome sequencing was performed on the HiSeq 2000 platform with paired-end reads of 101 bp in the three members. Results: We identified 19,436, 19,468, and 19,345 single-nucleotide polymorphisms (SNPs) in the coding regions. Among them, 8,759, 8,789, and 8,772 were non-synonymous SNPs, respectively. After filtering out 12,843 synonymous variations and 12,105 known variations with indels found in the dbSNP135 or 1000 Genomes Project database, we selected 73 variations in the samples from the affected sisters that did not occur in the sample from the unaffected mother. Using the Sorting Intolerant From Tolerant (SIFT), PolyPhen-2, and MutationTaster algorithms to predict amino acid substitutions, the XCR1, DLL1, TH, ACCS, SPPL3, CCNF, and SRL genes were risky among all three algorithms, while definite candidate genes could not be conclusively determined. Conclusion: Using exome sequencing, we found 7 variants for a breast cancer family without BRCA mutations. Genetic evidence of disease association should be confirmed by future studies.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8467-8471
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• 2016

Background: One of the major mechanisms for drug resistance is associated with altered anticancer drug transport, mediated by the human-adenosine triphosphate binding cassette (ABC) transporter superfamily proteins. The overexpression of adenosine triphosphate binding cassette, sub-family B, member 1 (ABCB1) by multidrug-resistant cancer cells is a serious impediment to chemotherapy. In our study we have studied the possibility that structural single-nucleotide polymorphisms (SNP) are the mechanism of ABCB1 overexpression. Materials and Methods: A total of 101 gastric cancer multidrug resistant cases and 100 controls were genotyped with sequence-specific primed PCR (SSP-PCR). Gene expression was evaluated for 70 multidrug resistant cases and 54 controls by real time PCR. The correlation between the two groups was based on secondary structures of RNA predicted by bioinformatics tool. Results: The results of genotyping showed that among 3 studied SNPs, rs28381943 and rs2032586 had significant differences between patient and control groups but there were no differences in the two groups for C3435T. The results of real time PCR showed over-expression of ABCB1 when we compared our data with each of the genotypes in average mode. Prediction of secondary structures in the existence of 2 related SNPs (rs28381943 and rs2032586) showed that the amount of ${\Delta}G$ for original mRNA is higher than the amount of ${\Delta}G$ for the two mentioned SNPs. Conclusions: We have observed that 2 of our studied SNPs (rs283821943 and rs2032586) may elevate the expression of ABCB1 gene, through increase in mRNA stability, while this was not the case for C3435T.

• 생물정신의학
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• 제24권1호
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• pp.32-38
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• 2017

Objectives This study was aimed to investigate the association between amisulpride-induced hyperprolactinemia and the Taq1A polymorphism in the D2 dopamine receptor gene (DRD2) in schizophrenic patients. Methods The plasma concentrations of prolactin were measured before and after treatment with amisulpride in one hundred and twenty-five schizophrenic patients. The effect of the Taq1A variants of the DRD2 on the risk of amisulpride-induced hyperprolactinemia was the main the outcome measure. The genotyping for Taq1A (rs1800497) polymorphism was performed using TaqMan single nucleotide polymorphism (SNP) genotyping assay. Results There was a significant difference between the prolactin level at baseline and the 6th week after treatment with amisulpride in all the subjects. However, there were no significant correlations between ΔProlactin (the difference between prolactin level at baseline and the 6th week after treatment) and the Taq1A genotypes. Conclusions This is the first study to investigate the-correlations between the Taq1A polymorphism and the amisulpride-induced hyperprolactinemia in Korean schizophrenic patients. The current results suggested the further large-scale researches on various SNPs in the DRD2 gene will establish clear goals and provide answers to the unanswered questions described in this study.

• BMB Reports
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• 제45권1호
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• pp.44-46
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• 2012

Recent advances in high-throughput genotyping technologies have enabled us to conduct a genome-wide association study (GWAS) on a large cohort. However, analyzing millions of single nucleotide polymorphisms (SNPs) is still a difficult task for researchers conducting a GWAS. Several difficulties such as compatibilities and dependencies are often encountered by researchers using analytical tools, during the installation of software. This is a huge obstacle to any research institute without computing facilities and specialists. Therefore, a proper research environment is an urgent need for researchers working on GWAS. We developed BioSMACK to provide a research environment for GWAS that requires no configuration and is easy to use. BioSMACK is based on the Ubuntu Live CD that offers a complete Linux-based operating system environment without installation. Moreover, we provide users with a GWAS manual consisting of a series of guidelines for GWAS and useful examples. BioSMACK is freely available at http://ksnp.cdc.go.kr/biosmack.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6005-6010
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• 2012

Background: Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian populations. Geographical and ethnic clustering of the cancer is due to genetic, environmental, and lifestyle risk factors. This case-control study aimed to identify or confirm both genetic and non-genetic risk factors for NPC in one of the endemic countries, Malaysia. Materials and Methods: A panel of 768 single-nucleotide polymorphisms (SNPs) previously associated with various cancers and known non-genetic risk factors for NPC were selected and analyzed for their associations with NPC in a case-control study. Results: Statistical analysis identified 40 SNPs associated with NPC risk in our population, including 5 documented previously by genome-wide association studies (GWAS) and other case-control studies; the associations of the remaining 35 SNPs with NPC were novel. In addition, consistent with previous studies, exposure to occupational hazards, overconsumption of salt-cured foods, red meat, as well as low intake of fruits and vegetables were also associated with NPC risk. Conclusions: In short, this study confirmed and/or identified genetic, environmental and dietary risk factors associated with NPC susceptibility in a Southeast Asian population.

• Asian-Australasian Journal of Animal Sciences
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• 제31권8호
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• pp.1127-1133
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• 2018

Objective: Genome wide association study was conducted to identify and validate candidate genes associated with fatty acid composition of pork. Methods: A total of 480 purebreed Duroc pigs were genotyped using IlluminaPorcine60k bead chips while the association test was implemented following genome-wide rapid association using Mixed Model and Regression-Genomic Control (GRAMMAR-GC) approach. Results: A total of 25, 29, and 16 single nucleotide polymorphisms (SNPs) were significantly associated with stearic (18:0), oleic (18:1) and saturated fatty acids (SFA), respectively. Genome wide significant variants were located on the same region of swine chromosome 14 (SSC14) that spanned from 120 to 124 Mb. Top SNP ALGA008191 was located at 5 kb near the stearoyl-CoA desaturase (SCD) gene. This gene is directly involved in desaturation of stearic acid into oleic acid. General relationship of significant SNPs showed high linkage disequilibrium thus genome-wide signals was attributed to SCD gene. However, understanding the role of other genes like elongation of very long chain fatty acids-3 (ELOVL3) located on this chromosomal segment might help in further understanding of metabolism and biosynthesis of fatty acids. Conclusion: Overall, this study provides evidence that validates SCD gene as strong candidate gene associated with fatty acid composition in Duroc pigs. Moreover, this study confirms significant SNPs near ELOVL3 gene.

• Genes and Genomics
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• 제40권12호
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• pp.1331-1338
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• 2018

Although there have been plenty of dominance deviation analysis, few studies have dealt with multiple phenotypes. Because researchers focused on multiple phenotypes (final weight and backfat thickness) of Landrace pigs, the classification of the genes was possible. With genome-wide association studies (GWASs), we analyzed the additive and dominance effects of the single nucleotide polymorphisms (SNPs). The classification of the pig genes into four categories (overdominance in final weight, overdominance in backfat thickness and overdominance in final weight, underdominance in backfat thickness, etc.) can enable us not only to analyze each phenotype's dominant effects, but also to illustrate the gene ontology (GO) analysis with different aspects. We aimed to determine the additive and dominant effect in backfat thickness and final weight and performed GO analysis. Using additive model and dominance deviation analysis in GWASs, Landrace pigs' overdominant and underdominant SNP effects in final weight and backfat thickness were surveyed. Then through GO analysis, we investigated the genes that were classified in the GWASs. The major GO terms of the underdominant effects in final weight and overdominant effects in backfat thickness were ion transport with the SLC8A3, KCNJ16, P2RX7 and TRPC3 genes. Interestingly, the major GO terms in the underdominant effects in the final weight and the underdominant effects in the backfat thickness were the regulation of ion transport with the STAC, GCK, TRPC6, UBASH3B, CAMK2D, CACNG4 and SCN4B genes. These results demonstrate that ion transport and ion transport regulation genes have distinct dominant effects. Through GWASs using the mode of linear additive model and dominance deviation, overdominant effects and underdominant effects in backfat thickness was contrary to each other in GO terms (ion transport and ion transport regulation, respectively). Additionally, because ion transport and ion transport regulation genes are associative with adipose tissue accumulation, we could infer that these two groups of genes had to do with unique fat accumulation mechanisms in Landrace pigs.

• Genes and Genomics
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• 제40권12호
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• pp.1279-1285
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• 2018

Interdigitating dendritic cell sarcoma (IDCS) is an aggressive neoplasm and is an extremely rare disease, with a challenging diagnosis. Etiology of IDCS is also unknown and most studies with only case reports. In our case, immunohistochemistry showed that the tumor cells were positive for S100, CD45, and CD68, but negative for CD1a and CD21. This study aimed to investigate the causative factors of IDCS by sequencing the protein-coding regions of IDCS. We performed whole-exome sequencing with genomic DNA from blood and sarcoma tissue of the IDCS patient using the Illumina Hiseq 2500 platform. After that, we conducted Sanger sequencing for validation of sarcoma-specific variants and gene ontology analysis using DAVID bioinformatics resources. Through comparing sequencing data of sarcoma with normal blood, we obtained 15 nonsynonymous single nucleotide polymorphisms (SNPs) as sarcoma-specific variants. Although the 15 SNPs were not validated by Sanger sequencing due to tumor heterogeneity and low sensitivity of Sanger sequencing, we examined the function of the genes in which each SNP is located. Based on previous studies and gene ontology database, we found that POLQ encoding DNA polymerase theta enzyme and FNIP1 encoding tumor suppressor folliculin-interacting protein might have contributed to the IDCS. Our study provides potential causative genetic factors of IDCS and plays a role in advancing the understanding of IDCS pathogenesis.

• Asian-Australasian Journal of Animal Sciences
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• 제31권12호
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• pp.1863-1870
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• 2018

Objective: The Bayesian first-order antedependence models, which specified single nucleotide polymorphisms (SNP) effects as being spatially correlated in the conventional BayesA/B, had more accurate genomic prediction than their corresponding classical counterparts. Given advantages of $BayesC{\pi}$ over BayesA/B, we have developed hyper-$BayesC{\pi}$, ante-$BayesC{\pi}$, and ante-hyper-$BayesC{\pi}$ to evaluate influences of the antedependence model and hyperparameters for $v_g$ and $s_g^2$ on $BayesC{\pi}$.Methods: Three public data (two simulated data and one mouse data) were used to validate our proposed methods. Genomic prediction performance of proposed methods was compared to traditional $BayesC{\pi}$, ante-BayesA and ante-BayesB. Results: Through both simulation and real data analyses, we found that hyper-$BayesC{\pi}$, ante-$BayesC{\pi}$ and ante-hyper-$BayesC{\pi}$ were comparable with $BayesC{\pi}$, ante-BayesB, and ante-BayesA regarding the prediction accuracy and bias, except the situation in which ante-BayesB performed significantly worse when using a few SNPs and ${\pi}=0.95$. Conclusion: Hyper-$BayesC{\pi}$ is recommended because it avoids pre-estimated total genetic variance of a trait compared with $BayesC{\pi}$ and shortens computing time compared with ante-BayesB. Although the antedependence model in $BayesC{\pi}$ did not show the advantages in our study, larger real data with high density chip may be used to validate it again in the future.