• Environmental Analysis Health and Toxicology
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• v.21 no.1 s.52
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• pp.27-34
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• 2006

Numerous studies reported the significant association between genetic polymorphisms in the vitamin D receptor (VDR) gene and various bone phenotypes such as bone mineral density (BMD) and bone quality, although conflicting results were produced. The objective of this study was to investigate the association between a TaqI RFLP in the VDR gene and calcaneal BMD in Korean vegetarian men, and its interaction with nutrition status as an environmental factor. BUA (broadband ultrasound attenuation), SOS (sound of speed) and stiffness index of the calcaneus were measured using an ultrasound bone densitometer in 266 Korean men (age: $mean{\pm}SD;\;50.9{\pm}12.0$ year), and a TaqI RFLP in the VDR gene analysed by PCR-RFLP method. In total subjects, the distribution of TT, Tt and tt genotypes occurred with frequencies of 90.8%, 8.8% and 0.4%, respectively. There were no significant associations between this polymorphism and osteopenia-osteoporosis or several bone phenotypes in our subjects irrespectively of nutrition status (P>0.05). Therefore, our results suggest that a TaqI RFLP in the vitamin D receptor gene does not contribute to the susceptibility to the calcaneal BMD in Korean men.

• Molecules and Cells
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• v.40 no.7
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• pp.450-456
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• 2017

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-$erb{\alpha}$ induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

• Genomics & Informatics
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• v.8 no.3
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• pp.131-137
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• 2010

Genome-wide association studies (GWASs) have greatly contributed to the identification of common variants responsible for numerous complex traits. There are, however, unavoidable limitations in detecting causal and/or rare variants for traits in this approach, which depends on an LD-based tagging SNP microarray chip. In an effort to detect potential casual and/or rare variants for complex traits, such as type 2 diabetes (T2D) and triglycerides (TGs), we conducted a targeted resequencing of loci identified by the Korea Association REsource (KARE) GWAS. The target regions for resequencing comprised whole exons, exon-intron boundaries, and regulatory regions of genes that appeared within 1 Mb of the GWA signal boundary. From 124 individuals selected in population-based cohorts, a total of 0.7 Mb target regions were captured by the NimbleGen sequence capture 385K array. Subsequent sequencing, carried out by the Roche 454 Genome Sequencer FLX, generated about 110,000 sequence reads per individual. Mapping of sequence reads to the human reference genome was performed using the SSAHA2 program. An average of 62.2% of total reads was mapped to targets with an average 22X-fold coverage. A total of 5,983 SNPs (average 846 SNPs per individual) were called and annotated by GATK software, with 96.5% accuracy that was estimated by comparison with Affymetrix 5.0 genotyped data in identical individuals. About 51% of total SNPs were singletons that can be considered possible rare variants in the population. Among SNPs that appeared in exons, which occupies about 20% of total SNPs, 304 nonsynonymous singletons were tested with Polyphen to predict the protein damage caused by mutation. In total, we were able to detect 9 and 6 potentially functional rare SNPs for T2D and triglycerides, respectively, evoking a further step of replication genotyping in independent populations to prove their bona fide relevance to traits.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.2
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• pp.83-87
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• 2008

The fyn-related kinase (FRK) belongs to the tyrosine kinase family of protein kinases. Recent studies have shown that Frk affects pancreatic beta cell number during embryogenesis and promotes beta cell cytotoxic signals in response to streptozotocin. To investigate the genetic association between FRK polymorphisms and the risk of obesity in Korean population, single nucleotide polymorphisms (SNPs) in the FRK gene region were selected and analyzed. The body mass index (BMI) was calculated, and biochemical data (systolic blood pressure, diastolic blood pressure, hemoglobin A1C, triglyceride, total cholesterol, high density lipoprotein, and low density lipoprotein) of blood sample from each subject were also measured. One hundred fifty five healthy control and 204 overweight/obesity subjects were recruited. Genotype frequencies of six SNPs [rs6568920 (+8391G>A), rs3756772 (+56780A>G), rs3798234 (+75687C>T), rs9384970 (+68506G>A), rs1933739 (+72978G>A), and rs9400883 (+75809A>G)] in the FRK gene were determined by Affymetrix Targeted Genotyping Chip data. According to the classification of Korean Society for the Study of Obesity, control (BMI 18 to < 23) and overweight/obesity (BMI$\geq$23) subjects were recruited. For the analysis of genetic data, EM algorithm, SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used. Multiple logistic regression analysis (codominant, dominant, and recessive models) was performed. Age and gender as covariates were adjusted. For biochemical data, Student's t test was used. The mean value of BMI in the control and overweigh/obesity groups was 21.1${\pm}$1.2 (mean${\pm}$SD) and 25.6${\pm}$2.0, respectively. All biochemical data of the overweight/obesity group were statistically significance, compared with the control group. Among six SNPs, two linkage disequilibrium (LD) blocks were discovered. One block consisted of rs1933739 and rs9400883, and the other comprised rs3756772 and rs3798234. One SNP (rs9384970, +68506G>A) showed an association with overweight/obesity in the codominant model (p=0.03). Interestingly, the AA genotype distribution in the overweight/obesity group (n=7, 3.5%) was higher than those in the control group (n=1, 0.6%), which is not found in either Japanese or Chinese subjects. Therefore, the AA genotype of rs9384970 may be a risk factor for development of obesity in Korean population. The results suggest that FRK may be associated with overweight/obesity in Korean population.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6027-6032
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• 2015

Background: Polymorphisms of genes encoding PSCA, PLCE1 and MUC1 have been associated with the risk of different cancers in genome wide association studies (GWAS). Up to date there are limited data on the role of these genetic alterations in colorectal cancer (CRC) development. The aim of this study was to evaluate potential associations between single nucleotide polymorphisms (SNPs) of genes encoding PSCA, PLCE1 and MUC1 and the presence of CRC in European populations. Materials and Methods: Gene polymorphisms were analyzed in 574 European subjects (controls: n=382; CRC: n=192). PSCA C>T (rs2294008), PSCA G>A (rs2976392), MUC1 A>G (rs4072037) and PLCE1 A>G (rs2274223) SNPs were genotyped by RT-PCR. Results: The distribution of genotypes for all four SNPs was in line with the Hardy-Weinberg equilibrium (rs2294008, P=0.153; rs2976392, P=0.269; rs4072037, P=0.609; rs2274223, P=0.858). The distribution of genotypes and alleles of PSCA C>T, PSCA G>A, MUC1 A>G and PLCE1 A>G SNPs was similar among controls and CRC patient groups (P>0.05). GG genotype of MUC1 SNP was more frequent in CRC patients (24.0%) than in controls (20.2%); however, this association failed to reach significance (OR-1.45, P=0.15). Overall, in the present study SNPs of PSCA (rs2294008, rs2976392), MUC1 (rs4072037) and PLCE1 (rs2274223) genes were not associated with the presence of CRC. Conclusions: Gene polymorphisms of PSCA, PLCE1 and MUC1 genes are not associated with the presence of CRC in European subjects.

• Journal of Animal Science and Technology
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• v.53 no.4
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• pp.311-317
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• 2011

The aim of this study was to evaluate the association between economic traits of Korean cattle (Hanwoo) and genetic variation in fatty acid binding protein 5 (FABP5) gene within QTL region of carcass weight and marbling score traits on BTA 14. We sequenced for detection of single nucleotide polymorphism (SNP) with 24 unrelated Hanwoo samples and identified four SNPs (-1141A>G, 949A>G, 969A>G and 1085C>G). Relationship between the genotypes of 583 Hanwoo individuals by PCR-RFLP and economic traits were analyzed by the mixed regression model implemented in the ASReml program. As the result of statistical analysis, SNP1 (-1141A>G) showed significant effect (p<0.003) on marbling score (MS) and SNP2 (949A>G) showed significant effect (p<0.034) on eye muscle area (EMA). Further studies are required to validate the significant SNPs in a bigger population, but the SNPs (-1141A>G and 949A>G) of FABP5 could be a genetic marker to estimate molecular breeding value (MEBV) for carcass traits in Hanwoo.

• Proceedings of the Korean Society of Crop Science Conference
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• 2022.10a
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• pp.207-207
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• 2022

Eating and cooking quality (ECQ) is one of the most complex quantitative traits in rice. The understanding of genetic regulation of transcript expression levels attributing to phenotypic variation in ECQ traits is limited. We integrated whole-genome resequencing, transcriptome, and phenotypic variation data from 84 Japonica accessions to build a transcriptome-wide association study (TWAS) based regulatory network. All ECQ traits showed a large phenotypic variation and significant phenotypic correlations among the traits. TWAS analysis identified a total of 285 transcripts significantly associated with six ECQ traits. Genome-wide mapping of ECQ-associated transcripts revealed 66,905 quantitative expression traits (eQTLs), including 21,747 local eQTLs, and 45,158 trans-eQTLs, regulating the expression of 43 genes. The starch synthesis-related genes (SSRGs), starch synthase IV-1 (SSIV-1), starch branching enzyme 1 (SBE1), granule-bound starch synthase 2 (GBSS2), and ADP-glucose pyrophosphorylase small subunit 2a (OsAGPS2a) were found to have eQTLs regulating the expression of ECQ associated transcripts. Further, in co-expression analysis, 130 genes produced at least one network with 22 master regulators. In addition, we developed CRISPR/Cas9-edited glbl mutant lines that confirmed the role of alpha-globulin (glbl) in starch synthesis to validate the co-expression analysis. This study provided novel insights into the genetic regulation of ECQ traits, and transcripts associated with these traits were discovered that could be used in further rice breeding.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.145-150
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• 2014

MicroRNAs (miRNAs) negatively regulate gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to digestive system cancers was inconsistent in previous studies. In this study, we conducted a literature search of PubMed to identify all relevant studies published before August 31, 2013. A total of 21 independent case-control studies were included in this updated meta-analysis with 9,558 cases and 10,614 controls. We found that the miR-146a rs2910164 polymorphism was significantly associated with decreased risk of digestive system cancers in an allele model (OR=0.90, 95%CI 0.87-0.94), homozygote model (OR=0.84, 95%CI 0.77-0.91), dominant model (OR=0.90, 95%CI 0.84-0.96), and recessive model (OR=0.85, 95%CI 0.79-0.91), while in a heterozygous model (OR = 0.99, 95% CI 0.89-1.11) the association showed marginal significance. Subgroup analysis by cancer site revealed decreased risk in colorectal cancer above allele model (OR=0.90, 95%CI 0.83-0.97) and homozygote model (OR=0.85, 95%CI 0.72-1.00). Similarly, decreased cancer risk was observed when compared with allele model (OR=0.87, 95%CI 0.81-0.93) and recessive model (OR=0.81, 95%CI 0.72-0.90) in gastric cancer. When stratified by ethnicity, genotyping methods and quality score, decreased cancer risks were also observed. This current meta-analysis indicated that miR-146a rs2910164 polymorphism may decrease the susceptibility to digestive system cancers, especially in Asian populations.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5277-5281
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• 2014

Published studies have evaluated associations between the MDM2 SNP309T>G polymorphism and bladder cancer susceptibility. However, these generated inconsistent results. The aim of the present investigation was to quantify the strength of association between MDM2 SNP309T>G polymorphism and bladder cancer risk by conducting a meta-analysis. We searched PubMed and Embase for related studies that had been published in English before April 1, 2014 and associations were assessed by summarizing the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Five case-control studies with a total of 972 cases and 1,012 controls were finally identified to be eligible for the meta-analysis. Overall, the results indicated that there was no significant association between the MDM2 SNP309T>G polymorphism and bladder cancer risk (for the allele model G vs. T: OR=1.08, 95% CI 0.85-1.36, p=0.54; for the co-dominant model GG vs. TT: OR=1.20, 95% CI 0.74-1.93, p=0.46; for the dominant model GG+GT vs. TT: OR=0.98, 95% CI 0.80-1.20, p=0.83; for the recessive model GG vs. GT+TT: OR=1.20, 95% CI 0.83-1.74, p=0.33). However, on subgroup analysis by ethnicity, significant associations were found in Caucasians in three models (for the allele model G vs. T: OR=1.41, 95% CI 1.10-1.81, p=0.006; for the co-dominant model GG vs. TT: OR=2.16, 95% CI 1.28-3.63, p=0.004; for the recessive model GG vs. GT+TT: OR=2.06, 95% CI 1.31-3.22, p=0.002). In summary, the present meta-analysis provides evidence that the genotype for the MDM2 SNP309T>G polymorphism may be associated with genetic susceptibility to bladder cancer among Caucasians.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.4
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• pp.462-469
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• 2017

Objective: The aim of this study is to identify genomic regions or genes controlling growth traits in pigs. Methods: Using a panel of 54,148 single nucleotide polymorphisms (SNPs), we performed a genome-wide Association (GWA) study in 562 pure Yorshire pigs with four growth traits: average daily gain from 30 kg to 100 kg or 115 kg, and days to 100 kg or 115 kg. Fixed and random model Circulating Probability Unification method was used to identify the associations between 54,148 SNPs and these four traits. SNP annotations were performed through the Sus scrofa data set from Ensembl. Bioinformatics analysis, including gene ontology analysis, pathway analysis and network analysis, was used to identify the candidate genes. Results: We detected 6 significant and 12 suggestive SNPs, and identified 9 candidate genes in close proximity to them (suppressor of glucose by autophagy [SOGA1], R-Spondin 2 [RSPO2], mitogen activated protein kinase kinase 6 [MAP2K6], phospholipase C beta 1 [PLCB1], rho GTPASE activating protein 24 [ARHGAP24], cytoplasmic polyadenylation element binding protein 4 [CPEB4], GLI family zinc finger 2 [GLI2], neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adaptor 2 [NYAP2], and zinc finger protein multitype 2 [ZFPM2]). Gene ontology analysis and literature mining indicated that the candidate genes are involved in bone, muscle, fat, and lung development. Pathway analysis revealed that PLCB1 and MAP2K6 participate in the gonadotropin signaling pathway and suggests that these two genes contribute to growth at the onset of puberty. Conclusion: Our results provide new clues for understanding the genetic mechanisms underlying growth traits, and may help improve these traits in future breeding programs.