Association Of Sequence Variants Research Articles

BART-D2 subtype of EBV encoded BART miRNA cluster 1 region is strongly associated with endemic nasopharyngeal carcinoma.

Epstein-Barr virus (EBV)-encoded BamHI A rightward transcript (BART) microRNAs (miRNAs) play important roles in viral infection and tumorigenesis. The association of sequence variations in the BART miRNA cluster 1 region with diseases remains unclear. Herein, 6 types and 11 subtypes of BART cluster 1 were identified in 354 tumors and healthy donors (HDs) from nasopharyngeal carcinoma (NPC)-endemic and nonendemic China (genotyped data), and 905 EBV genomes retrieved from GenBank from diseased and normal people from around the world (archived data). The distributions of BART cluster 1 types/subtypes between NPC-endemic and nonendemic China; between Asian regions and Africa/Europe & Australia & United States; and among Asian regions (NPC-endemic China, NPC-nonendemic East Asia and Southeast Asia) were significantly different (p < 0.001). The subtype BART-D2 was not found outside Asia and was only common in NPC-endemic China. More importantly, BART-D2 had a higher frequency in NPCs than in HDs in NPC-endemic China (genotyped data, 78.0% vs. 44.1%, p < 0.001; achieved data, 89.3% vs. 43.7%, p < 0.001), and was also more frequent in NPCs than in HDs, gastric carcinomas, and lymphomas in NPC-nonendemic China (genotyped data, 27.9% vs. 1.9%, 2.4%, and 0.0%, p < 0.001). BART-D2 was preferentially linked with the high-risk subtypes for NPC previously reported, 162476C or 163364T, in the BALF2 gene, and was associated with NPC risk (p < 0.01). In vitro experiments showed that BART-D2 affected the expression of some mature BART miRNAs. These findings demonstrate geographically restricted variations of BART cluster 1 and identify distinct subtype that is confined to NPC-endemic China and is associated with NPC.

A Case-Control Study of the Association of Leptin Gene Polymorphisms with Plasma Leptin Levels and Obesity in the Kerala Population.

Over the last few years, the importance of leptin in energy metabolism has been extensively studied in both animal models and in humans. Very few results are available on the association between human leptin gene (LEP) variants and obesity traits in India. We designed this study to analyse the polymorphisms in human leptin gene and the association of sequence variants with obesity among the population in Kerala, South India. In this case-control design of 148 study participants, data were collected on socioeconomic aspects and anthropometric measurements. Plasma glucose, insulin, leptin, and lipid profile were measured. Genotyping was done by automated DNA sequencing. The common Single Nucleotide Polymorphism (SNP) of 5'-UTR of LEP - 2548G/A was found to be present in the study population with "A" variant as dominant allele. A novel synonymous mutation Thr5Thr of exon 2 of LEP was identified in heterozygous form in one subject with morbid obesity with hyperleptinemia. A novel missense mutation Phe17Leu was observed in two subjects with obesity in heterozygous condition. A novel missense mutation Lys36Arg in exon 2 of LEP was observed in one subject with abdominal obesity and decreased serum leptin level. LEP - 2548G/A at 5'-untranslated region was found to be common with the mutant "A" variant in the study population. SNPs of exons in LEP were found to be rare but associated with morbid obesity and altered levels of serum leptin in the study population in Kerala, India.

Sequence variants in the renin-angiotensin system genes are associated with isolated multicystic dysplastic kidney in children.

Multicystic dysplastic kidney (MCDK) is a common form of congenital cystic kidney disease in children. The etiology of MCDK remains unclear. Given an important role of the renin-angiotensin system in normal kidney development, we explored whether MCDK in children is associated with variants in the genes encoding renin-angiotensin system components by Sanger sequencing. The coding regions of renin (REN), angiotensinogen (AGT), ACE, and angiotensin 1 receptor (AGTR1) genes were amplified by PCR. The effect of DNA sequence variants on protein function was predicted with PolyPhen-2 software. 3 novel and known AGT variants were found. 1 variant was probably damaging, 1 was possibly damaging and one was benign. Out of 7 REN variants, 4 were probably damaging and 3 were benign. Of 6 ACE variants, 3 were probably damaging and 3-benign. 3 AGTR1 variants were found. 2 variants were possibly damaging, and one was benign. We report novel associations of sequence variants in REN, AGT, ACE, or AGTR1 genes in children with isolated MCDK in the United States. Our findings suggest a recessive disease model and support the hypothesis of multiple renin-angiotensin system gene involvement in MCDK. Discovery of novel gene variants in renin-angiotensin genes in children with MCDK. Novel possibly damaging gene variants discovered. Multiple renin-angiotensin system gene variants are involved in MCDK.

Association of Sequence Variants in the CKM (Creatine Kinase, M-Type) Gene with Racing Performance of Homing Pigeons

Association of Sequence Variants in the CKM (Creatine Kinase, M-Type) Gene with Racing Performance of Homing Pigeons

Expression profiles of the MXD3 gene and association of sequence variants with growth traits in Xianan and Qinchuan cattle.

Max dimerization protein 3 (MXD3) belongs to the MYC superfamily of basic helix‐loop‐helix leucine zipper transcription factors, and MXD3‐MAX heterodimers can bind to promoters of target genes to modulate their expression. The aim of this study was to determine the MXD3 mRNA expression levels in various cattle tissues comprising heart, liver, spleen, lung, kidney, Longissimus dorsi muscle and subcutaneous fat in Chinese Qinchuan and Xianan cattle breeds. The RT‐qPCR data showed that the MXD3 gene was variably expressed between all tissues and at levels that were significantly different between two breeds (p < .05). We used the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method to investigate the possible association between single‐nucleotide polymorphisms (SNP) within the MXD3 gene and five different growth traits in cattle. We found two intronic SNPs (g.2694 C>T and g.3801 T>C) and one SNP in 3′untranslated region (3′UTR) (g.6263 G>A) of MXD3 gene. Association analysis revealed strong associations between pairwise and triple SNP combinations and the growth traits. Based on these results, we suggest that MXD3 polymorphisms could be useful as molecular markers in the Chinese beef cattle breeding program.

Polymorphism in the ovine keratin-associated protein gene KRTAP7-1 and its association with wool characteristics.

The keratin-associated proteins (KAPs) are structural components of wool fibers and variation in the genes encoding the KAPs can affect wool traits. In this study, sequence variation in the ovine KAP7-1 gene (KRTAP7-1) was investigated in 222 sheep across 5 different Pakistani breeds and breed crosses. Two previously identified variants (A and B) of the KRTAP7-1 coding sequence were identified. The frequency of the genotypes AA and AB was 76% and 23%, respectively, and that of BB was 1%. The association of sequence variation with various wool traits and measurements included yield (the proportion of greasy fleece weight that is clean fleece), mean staple length (MSL), wool bulk, mean fiber diameter, fiber diameter SD, the coefficient of variation of fiber diameter, medullation, the SD of medullation, the coefficient of variation of medullation, fiber opacity, the SD of opacity, and the coefficient of variation of opacity. Variation in KRTAP7-1 was found to be associated with yield (P = 0.017). The adjusted mean yield of sheep of genotype AA (n = 169) was 79.9 ± 2.72%, while that of genotype AB (n = 51) was 81.9 ± 3.37%. There was also an association between variation in KRTAP7-1 and MSL (P = 0.024), with sheep of genotype AA (n = 169) having an adjusted mean MSL of 47.3 ± 0.57 mm compared with sheep of genotype AB (n = 51, 50.9 ± 0.65 mm). Yield and MSL are both important wool production traits, hence variation in KRTAP7-1 needs to be further investigated in more sheep of differing breed.

Identification of Sequence Variants within Experimentally Validated Protein Interaction Sites Provides New Insights into Molecular Mechanisms of Disease Development.

Protein interactions (PI) underlie complex biological processes. Protein interaction partners include DNA, RNA, ions, small chemical compounds, and proteins (protein-protein interactions; PPI). Analysis of sequence variants within regions corresponding to experimentally validated PI sites presents novel opportunities for understanding of complex diseases. Such information has not been systematically collected due to the fact that datasets are dispersed throughout databases and publications. Sequence variants and PI regions were obtained from the UniProt database. The location of the variants was compared to start and end positions of each PPI. Associations of sequence variants with phenotype were obtained from databases including COSMIC, GAD, PharmGKB, and dbSNP. We developed a catalogue of 603 sequence variants located within regions corresponding to experimentally validated PI sites, mostly PPI regions. These sequence variants were previously associated with risk for cancer, reproduction, ageing, renal, and immune system diseases. The developed catalogue connects information from different research papers and databases, represents a new layer of information and enables designing new hypotheses. It provides a baseline for prioritization of sequence variants, which may affect protein function and binding sites. The study contributes to the development of the proteogenomics field and provides new insights for understanding molecular mechanisms underlying disease development.

Mitochondrial DNA sequence data reveals association of haplogroup U with psychosis in bipolar disorder

Converging genetic, postmortem gene-expression, cellular, and neuroimaging data implicate mitochondrial dysfunction in bipolar disorder. This study was conducted to investigate whether mitochondrial DNA (mtDNA) haplogroups and single nucleotide variants (SNVs) are associated with sub-phenotypes of bipolar disorder. MtDNA from 224 patients with Bipolar I disorder (BPI) was sequenced, and association of sequence variations with 3 sub-phenotypes (psychosis, rapid cycling, and adolescent illness onset) was evaluated. Gene-level tests were performed to evaluate overall burden of minor alleles for each phenotype. The haplogroup U was associated with a higher risk of psychosis. Secondary analyses of SNVs provided nominal evidence for association of psychosis with variants in the tRNA, ND4 and ND5 genes. The association of psychosis with ND4 (gene that encodes NADH dehydrogenase 4) was further supported by gene-level analysis. Preliminary analysis of mtDNA sequence data suggests a higher risk of psychosis with the U haplogroup and variation in the ND4 gene implicated in electron transport chain energy regulation. Further investigation of the functional consequences of this mtDNA variation is encouraged.

Association of Sequence Variation in the CX3CR1 Gene with Geographic Atrophy Age-related Macular Degeneration in a Greek Population

Purpose: To explore the association of two single nucleotide polymorphisms (SNPs) in the CX3CR1 gene with grades of age-related macular degeneration (AMD) in a population-based setting.Methods: The Thessaloniki Eye study is a cross-sectional population-based epidemiologic study of chronic eye diseases in Thessaloniki, Greece. A total of 371 subjects were included and classified according to their AMD status. Subjects with AMD Grades 0–1 (n = 188) were compared to those with AMD Grades 2–3 (n = 138), to those with AMD Grade 4 (geographic atrophy) (n = 20) and to those with AMD Grade 5 (neovascular AMD) (n = 25) with regard to the presence of CX3CR1 polymorphisms (V249I and T280M). Polychotomous logistic regression analysis adjusted for age, gender, and smoking was conducted and the log-additive allelic model was preferred.Results: Participants with AMD Grade 4 were approximately three times more likely to carry the VI249 and nine times more likely to carry the II249 alleles, compared to those with AMD Grades 0–1, whereas those with AMD Grades 2–3 or Grade 5 did not differ. The T280M polymorphism was not associated with either AMD Grades 2–3 or AMD Grades 4 or 5.Conclusion: In this Greek population, after adjusting for known risk factors, increased risk of geographic atrophy (GA) AMD among the carriers of the V249I polymorphism in the CX3CR1 gene was found. Our study failed to reveal any association with the T280M polymorphism reported in previous studies. Additional studies in different ethnic populations using standardized methodology are needed in order to confirm this association.

Association of Sequence Variants on Chromosomes 20, 11, and 5 (20q13.33, 11q23.3, and 5p15.33) With Glioma Susceptibility in a Chinese Population

Two genome-wide association studies of glioma in European populations identified 14 genetic variants strongly associated with risk of glioma, but it is unknown whether these variants are associated with glioma risk in Asian populations. The authors genotyped these 14 variants in 976 glioma patients and 1,057 control subjects to evaluate their associations with risk of glioma, particularly high-grade glioma (glioblastoma; n = 312), in a Chinese population (2004-2009). Overall, the authors identified 3 susceptibility loci for glioma risk at 20q13.33 (RTEL1 rs6010620 (P = 2.79 × 10(-6))), 11q23.3 (PHLDB1 rs498872 (P = 3.8 × 10(-6))), and 5p15.33 (TERT rs2736100 (P = 3.69 × 10(-4))) in this study population; these loci were also associated with glioblastoma risk (20q13.33: RTEL1 rs6010620 (P = 3.57 × 10(-7)); 11q23.3: PHLDB1 rs498872 (P = 7.24 × 10(-3)); 5p15.33: TERT rs2736100 and TERT rs2736098 (P = 1.21 × 10(-4) and P = 2.84 × 10(-4), respectively)). This study provides further evidence for 3 glioma susceptibility regions at 20q13.33, 11q23.3, and 5p15.33 in Chinese populations.

Association of sequence variants inCKM(creatine kinase, muscle) andCOX4I2(cytochrome c oxidase, subunit 4, isoform 2) genes with racing performance in Thoroughbred horses

The wild progenitors of the domestic horse were subject to natural selection for speed and stamina for millennia. Uniquely, this process has been augmented in Thoroughbreds, which have undergone at least 3 centuries of intense artificial selection for athletic phenotypes. While the phenotypic adaptations to exercise are well described, only a small number of the underlying genetic variants contributing to these phenotypes have been reported. A panel of candidate performance-related genes was examined for DNA sequence variation in Thoroughbreds and the association with racecourse performance investigated. Eighteen candidate genes were chosen for their putative roles in exercise. Re-sequencing in Thoroughbred samples was successful for primer sets in 13 of these genes. SNPs identified in this study and from the EquCab2.0 SNP database were genotyped in 2 sets of Thoroughbred samples (n = 150 and 148) and a series of population-based case-control investigations were performed by separating the samples into discrete cohorts on the basis of retrospective racecourse performance. Twenty novel SNPs were detected in 3 genes: ACTN3, CKM and COX4I2. Genotype frequency distributions for 3 SNPs in CKM and COX4I2 were significantly (P < 0.05) different between elite Thoroughbreds and racehorses that had never won a race. These associations were not validated when an additional (n = 130) independent set of samples was genotyped, but when analyses included all samples (n = 278) the significance of association at COX4I2 g.22684390C > T was confirmed (P < 0.02). While molecular genetic information has the potential to become a powerful tool to make improved decisions in horse industries, it is vital that rigour is applied to studies generating these data and that adequate and appropriate sample sets, particularly for independent replication, are used.

Sequence Variations in Mitochondrial Ferritin: Distribution in Healthy Controls and Different Types of Patients

The storage of iron in the cells is mainly accomplished by cytosolic ferritins. The perturbation of ferritin function may result in accumulation of excess iron in cells and tissues and increased oxidative stress, common features of different genetic and acquired disorders. Mutations in L-ferritin have been associated with neuroferritinopathy, a rare and severe movement disorder with abnormal brain iron storage. Recently, a novel form of ferritin has been discovered, which localizes in the mitochondrial matrix and plays an important role in iron homeostasis in these organelles. The possible association of sequence variations in the mitochondrial ferritin (FtMt) gene with disorders with aberrant iron distribution has not been investigated yet. We set up a denaturing high-performance liquid chromatography (DHPLC)-based screening for FtMt and analyzed the genomic DNA of patients with myelodysplastic syndromes (# 63) or with Parkinson's disease (# 332) and other movement disorders such as pantothenate kinase-associated neurodegeneration (# 7), restless legs syndrome (# 23), and suspected neuroferritinopathy (# 7) and of control subjects (# 342). We detected eight different types of substitution, all at the heterozygous state. Six of them caused amino acid changes, but none of them was predicted to drastically perturb FtMt structure and/or function. The c + 134C > A (P45H) variation, which was the most common (# 28), was less represented in the Parkinson's population, although not significantly (p = 0.07). The analysis suggests that sequence variations in the coding region of FtMt are not involved in the development of myelodysplastic syndromes and Parkinson's disease.

Association of sequence variation in Brassica GLABRA1 orthologs with leaf hairiness

A 5-bp deletion in exon 3 of a Brassica rapa ortholog of GLABRA1 (BrGL1) was previously thought to be responsible for the hairless trait of a doubled haploid line. In this study, the sequence variation of Brassica GL1 was characterized. The DNA-binding domain of GL1 in Arabidopsis thaliana was found to be highly conserved in Brassica species, while in hairless B. oleracea lines, frameshifts and nonsynonymous substitutions were detected in the coding sequences of BoGL1. Phylogenetic analysis showed that BnGL1 in hairless B. napus lines is closely related to BiGL1 in a hairy B. incana line. In 11 lines of B. rapa germplasm, nucleotide polymorphisms were only detected in exon 3 of BrGL1. Regarding the nucleotide polymorphisms in the DNA-binding domain of BrGL1, four alleles were identified, and corresponding dot-blot single nucleotide polymorphism (SNP) markers were developed and used for genotyping of 63 lines of B. rapa. The genotyping results showed that nucleotide polymorphisms in the DNA-binding domain of BrGL1 are associated with leaf hairiness. Reverse-transcription PCR analysis indicated that different BrGL1 alleles are all expressed normally. These findings reveal the key nucleotide polymorphisms of BrGL1 affecting leaf hairiness in the natural B. rapa population.

Analysis of lipid pathway genes indicates association of sequence variation near SREBF1/TOM1L2/ATPAF2 with dementia risk

We conducted dense linkage disequilibrium (LD) mapping of a series of 25 genes putatively involved in lipid metabolism in 1567 dementia cases [including 1270 with Alzheimer disease (AD)] and 2203 Swedish controls. Across a total of 448 tested genetic markers, the strongest evidence of association was as anticipated for APOE (rs429358 at P approximately 10(-72)) followed by a previously reported association of ABCA1 (rs2230805 at P approximately 10(-8)). In the present study, we report two additional markers near the SREBF1 locus on chromosome 17p that were also significant after multiple testing correction (best P = 3.1 x 10(-6) for marker rs3183702). There was no convincing evidence of association for remaining genes, including candidates highlighted from recent genome-wide association studies of plasma lipids (CELSR2/PSRC1/SORT1, MLXIPL, PCSK9, GALNT2 and GCKR). The associated markers near SREBF1 reside in a large LD block, extending more than 400 kb across seven candidate genes. Secondary analyses of gene expression levels of candidates spanning the LD region together with an investigation of gene network context highlighted two possible susceptibility genes including ATPAF2 and TOM1L2. Several markers in strong LD (r(2) > 0.7) with rs3183702 were found to be significantly associated with AD risk in recent genome-wide association studies with similar effect sizes, providing independent support of the current findings.

The associations of sequence variants in DNA-repair and cell-cycle genes with cancer risk: genotype–phenotype correlations

DNA-repair systems maintain the integrity of the human genome, and cell-cycle checkpoints are a critical component of the cellular response to DNA damage. Thus the presence of sequence variants in genes involved in these pathways that modulate their activity might have an impact on cancer risk. Many molecular epidemiological studies have investigated the association between sequence variants, particularly SNPs (single nucleotide polymorphisms), and cancer risk. For instance, ATM (ataxia telangiectasia mutated) SNPs have been associated with increased risk of breast, prostate, leukaemia, colon and early-onset lung cancer, and the intron 3 16-bp repeat in TP53 (tumour protein 53) is associated with an increased risk of lung cancer. In contrast, the variant allele of the rare CHEK2 (checkpoint kinase 2 checkpoint homologue) missense variant (accession number rs17879961) was significantly associated with a lower incidence of lung and upper aerodigestive cancers. For some sequence variants, a strong gene-environment interaction has also been noted. For instance, a greater absolute risk reduction of lung and upper aerodigestive cancers in smokers than in non-smokers carrying the I157T CHEK2 variant has been observed, as has an interaction between TP53 intron 3 16-bp repeats and multiple X-ray exposures on lung cancer risk. The challenge now is to understand the molecular mechanisms underlying these associations.

Association of Sequence Variations in Vitamin K Epoxide Reductase and γ-Glutamyl Carboxylase Genes with Biochemical Measures of Vitamin K Status

Genetic factors, specifically the VKORC1 and GGCX genes, have been shown to contribute to the interindividual variability in response to the vitamin K-antagonist, warfarin, which influences the dose required to achieve the desired anticoagulation response. These differences in warfarin sensitivity may be explained by differences in vitamin K status. Men and women (n=416, 60-80 y), primarily of European descent, were genotyped for common polymorphisms in VKORC1 and GGCX. Cross-sectional associations exist between polymorphisms and biochemical markers of vitamin K [plasma phylloquinone, percent undercarboxylated osteocalcin (%ucOC)]. VKORC1 rs8050894 GG homozygotes had significantly higher cross-sectional measures of plasma phylloquinone than carriers of the CG or CC genotypes (plasma phylloquinone geometric means: GG 0.874+/-0.092 versus CG/CC 0.598+/- 0.044; p=0.020), whereas carriers of VKORC1 rs7294 AA or AG had significantly lower plasma phylloquinone concentrations compared to GG homozygotes (plasma phylloquinone geometric means: 0.579+/-0.045 versus 0.762+/-0.057; p=0.035). Cross-sectional analyses also revealed that heterozygous carriers of GGCX rs10187424 and rs7568458 had significantly lower %ucOC relative to either homozygous group. Polymorphisms in genes encoding enzymes involved in vitamin K metabolism may modulate plasma concentrations of phylloquionone and percent carboxylation of osteocalcin.

Association of sequence variations in the gene encoding insulin-like growth factor binding protein 5 with adiponectin

Insulin-like growth factor binding protein 5 (IGFBP5) binds to IGF and thus modulates IGF signaling pathway. We have shown earlier that the IGFBP5 gene was downregulated in the adipose tissue after 12-week carbohydrate diet with low insulinemic response. The aim was to examine the putative contribution of genetic variation of the IGFBP5 gene to the characteristics of metabolic syndrome and incidence of type 2 diabetes (T2DM) in the Finnish Diabetes Prevention Study (DPS). DPS is a longitudinal study where 522 subjects with impaired glucose tolerance were randomized to either lifestyle intervention group or control group. DNA was available from 507 subjects (mean body mass index (BMI) 31.2+/-4.5 kg/m(2), age 55+/-7 years). The eight single-nucleotide polymorphisms (SNPs) were selected from HapMap database and genotyped by Taqman allelic discrimination protocol. The main results were confirmed in a larger cross-sectional study population (METSIM). In addition, the gene expression of IGFBP5 was studied in two previously published study populations (FUNGENUT and GENOBIN) of 124 subjects with insulin resistance (BMI 32.2+/-3.5 kg/m(2), age 57.7+/-7.4 years). Three out of eight IGFBP5 markers (rs9341234, rs3276 and rs11575134) were significantly associated with circulating adiponectin concentrations in men. Furthermore, mRNA expression studies of subcutaneous adipose tissue showed that mRNA concentrations of IGFBP5 correlated with adiponectin concentrations in all subjects and in women. None of the IGFBP5 SNPs were associated with T2DM. Our findings show that IGFBP5 has a gender-specific association with adiponectin, which may modulate the development of metabolic syndrome.

Genetic variation and gene expression in antioxidant related enzymes and risk of COPD: a systematic review

Background:Observational epidemiological studies of dietary antioxidant intake, serum antioxidant concentration and lung outcomes suggest that lower levels of antioxidant defences are associated with decreased lung function. Another approach to understanding...

No Association of Sequence Variants in the Neuropeptide Y2 Receptor (NPY2R) Gene with Early Onset Obesity in Germans

The neuropeptide Y2 receptor (NPY2R) has been implicated in body weight regulation both in humans and rodents. We investigated if genetic variation in the NPY2R gene is associated with obesity in German extremely obese children and adolescents. The coding sequence and predicted promoter of the NPY2R were screened for variations. Subsequently, case-control (184 extremely obese children and adolescents: mean body mass index [BMI] 35.7+/-6.1 kg/m(2), 277 lean students: mean BMI 18.2+/-1.1 kg/m(2)) and family-based (770 parental pairs with a total of 1081 obese off-spring) association analyses were conducted in independent samples. We identified 14 sequence variants (seven novel variants including two coding variants c.369C >T and c.834G >A), five of which were detected once, each in the heterozygous state. In case-control analyses we did not detect association with obesity for seven common (minor allele frequency >1%) variants (all p >0.16); additional gender-stratified analyses employing several genetic models and haplotype analyses were also nonsignificant. Furthermore, in a family-based association study for coding synonymous SNP rs1047214 (Ile195) we found no evidence for a transmission disequilibrium in the total or in the gender-stratified PDT analyses (all p >0.50). In conclusion, we did not find evidence for an involvement of genetic variation in the NPY2R in early onset obesity in German samples.

Association of Sequence Variations in DGAT 1 Gene with Economic Traits in Hanwoo (Korea Cattle)

The effects of diacylglycerol O-acyltransferase (DGAT1) candidate gene polymorphism on the economic traits of Hanwoo were studied. Through sequencing analysis, two polymorphism sites at K232A and T11993C were established and were analyzed by PCR-RFLP. The PCR-RFLP analysis for K232A showed that the frequencies of alleles K and A were 0.75 and 0.25, respectively, and the frequencies of genotypes for K/K, K/A and A/A were estimated as 0.509, 0.491 and 0, respectively. In the PCR-RFLP analysis for T11993C, we found allele frequencies of 0.773 and 0.227 for T and A, respectively, and 0.546, 0.454 and 0 for the T/T, T/C and C/C genotype frequencies, respectively. No significant effects on economic traits in Hanwoo were found in the separate analysis of K232A and T11993C polymorphisms, but the interaction between K232A and T11993C showed a significant effect (p<0.005) on marbling score. The DGAT1 candidate gene was found to have a significant effect not only on milk yield and component traits but also on the metabolism of intramuscular fat.