• Nutrition Research and Practice
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• v.9 no.1
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• pp.79-86
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• 2015

BACKGROUND/OBJECTIVES: It is well-known that alcohol consumption is associated with stroke risk as well as with aldehyde dehydrogenase 2 gene (ALDH2) polymorphisms. However, it is unclear whether ALDH2 polymorphisms are associated with stroke risk independent of alcohol consumption and whether such association is modified by sex. We evaluated sex-specific associations of a common ALDH2 polymorphism and alcohol consumption with stroke risk in a Korean population. SUBJECTS/METHODS: We conducted a prospective cohort study involving 8,465 men and women, aged 40-69 years and free of stroke between June, 2001 and January, 2003, and followed for the development of stroke. We identified new cases of stroke, which were self-reported or ascertained from vital registration data. Based on genome-wide association data, we selected a single-nucleotide polymorphism (rs2074356), which shows high linkage disequilibrium with the functional polymorphism of ALDH2. We conducted Cox proportional hazards regression analysis considering potential risk factors collected from a baseline questionnaire. RESULTS: Over the median follow-up of 8 years, 121 cases of stroke were identified. Carrying the wild-type allele of the ALDH2 polymorphism increased stroke risk among men. The multivariate hazard ratio [95% confidence interval] of stroke was 2.02 [1.03-3.99] for the wild-type allele compared with the mutant alleles, but the association was attenuated after controlling for alcohol consumption. Combinations of the wild-type allele and other risk factors of stroke, such as old age, diabetes mellitus, and habitual snoring, synergistically increased the risk among men. Among women, however, the ALDH2 polymorphism was not associated with stroke risk. CONCLUSIONS: The prospective cohort study showed a significant association between a common ALDH2 polymorphism and stroke risk in Korean men, but not in Korean women, and also demonstrated that men with genetic disadvantages gain more risk when having risk factors of stroke. Thus, these men may need to make more concerted efforts to control modifiable risk factors of stroke.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.9
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• pp.1345-1354
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• 2014

Copy number variations (CNVs), important genetic factors for study of human diseases, may have as large of an effect on phenotype as do single nucleotide polymorphisms. Indeed, it is widely accepted that CNVs are associated with differential disease susceptibility. However, the relationships between CNVs and gene expression have not been characterized in the horse. In this study, we investigated the effects of copy number deletion in the blood and muscle transcriptomes of Thoroughbred racing horses. We identified a total of 1,246 CNVs of deletion polymorphisms using DNA re-sequencing data from 18 Thoroughbred racing horses. To discover the tendencies between CNV status and gene expression levels, we extracted CNVs of four Thoroughbred racing horses of which RNA sequencing was available. We found that 252 pairs of CNVs and genes were associated in the four horse samples. We did not observe a clear and consistent relationship between the deletion status of CNVs and gene expression levels before and after exercise in blood and muscle. However, we found some pairs of CNVs and associated genes that indicated relationships with gene expression levels: a positive relationship with genes responsible for membrane structure or cytoskeleton and a negative relationship with genes involved in disease. This study will lead to conceptual advances in understanding the relationship between CNVs and global gene expression in the horse.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.85-91
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• 2014

Background: Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations. Methods: Ten SNPs (rs2075555 in COL1A1, rs12652447 in FBXL17, rs10941679 in 5p12/MRPS30, rs11878583 in ZNF577, rs7166081 in SMAD3, rs16917302 in ZNF365, rs311499 in 20q13.3, rs1045485 in CASP8, rs12964873 in CDH1 and rs8170 in 19p13.1) were here genotyped in 1009 Chinese females (487 patients with breast cancer and 522 control subjects) using the Sequenom MassARRAY iPLEX platform. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each SNP. Stratification analyses were carried out based on the estrogen receptor (ER) and progesterone receptor (PR) status. Results: Among the 10 SNPs, rs10941679 showed significant association with breast cancer when differences between the case and control groups in this Han Chinese population were compared (30.09% GG, 45.4% GA and 23.7% AA; P = 0.012). Four SNPs (rs311499, rs1045485, rs12964873 and rs8170) showed no polymorphisms in our study. The remaining five SNPs showed no association with breast cancer in the present population. Immunohistochemical tests showed that rs2075555 was associated with ER status; the AA genotype showed greater association with ER negative than ER positive (OR = 0.54, 95% CI, 0.29-0.99; P = 0.046). AA of rs7166081 was also associated with ER status, but showed a greater association with ER positive than negative (OR = 1.59, 95% CI = 1.04-2.44; P = 0.031). However, no significant associations were found among the SNPs and PR status. Conclusion: In this study using a Han Chinese population, rs10941679 was the only SNP associated with breast cancer risk, indicating a difference between European and Chinese populations in susceptibility loci. Therefore, confirmation studies are necessary before utilization of these loci in Chinese.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.299-304
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• 2014

Cholangiocarcinoma (CCA), a malignancy of biliary duct with a very poor prognosis, is the leading cause of cancer death in countries of the Mekong subregion. Liver fluke infection is the main etiological factor, but genetic variation has been recognized as also important in conferring susceptibility to CCA risk. Nuclear factor (erythroid derived 2)-like 2 (NRF2) is a key transcription factor in detoxification and antioxidant defense. Emerging evidence has demonstrated that genetic polymorphisms in the NRF2 gene may be associated with cancer development. The objectives of this study were to investigate the association of NRF2 genetic polymorphism with CCA risk and to evaluate the influence of the NRF2 genotype on survival time of affected patients. Single nucleotide polymorphisms (SNPs) of the NRF2 gene, including rs6726395: A/G, rs2886161: C/T, rs1806649: C/T, and rs10183914: C/T, were analyzed using TaqMan$^{(R)}$ SNP genotyping assays. Among 158 healthy northeastern Thai subjects, the allele frequencies were 41, 62, 94, and 92%, respectively. The correlation of NRF2 SNPs and CCA risk was analyzed in the 158 healthy subjects and 198 CCA patients, using unconditional logistic regression. The results showed that whereas the NRF2 SNPs were not associated with CCA risk (p>0.05), Kaplan-Meier analysis of 88 intrahepatic CCA patients showed median survival time with rs6726395 genotypes of GG and AA/AG to be $344{\pm}138$ (95%CI: 73-615) days and $172{\pm}37$ (95%CI: 100-244) days, respectively, (p<0.006). On multivariate Cox proportional hazard analysis, the GG genotype of rs6726395 was found to be associated with longer survival with a hazard ratio of 0.54 (95%CI: 0.31-0.94). In addition, non-papillary adenocarcinoma was associated with poor survival with a hazard ratio of 2.09 (95%CI: 1.16-3.75). The results suggest that the NRF2 rs6726395 polymorphism can be a potential prognostic biomarker for CCA patients.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.205-209
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• 2008

Recently, Sun et al (2008) reported that the IL6R polymorphism is associated with schizophrenia. Therefore, to detect the association between polymorphisms of interleukin 31 receptor A (IL31RA) and schizophrenia, we genotyped 9 SNPs [rs9292101 (intron 1), rs1009639 (exon 2, Pr043Pro), rs2161582 (intron 2), rs68761890 (intron 5), rs16884629 (intron 6), rs11956465 (intron 12), rs12153724 (intron 12), and rs16884641 (intron 14)] using the Golden Gate assay on Illumina BeadStation 500 GX. Two hundred eighteen patients with schizophrenia and 379 normal subjects were recruited. Patients with schizophrenia were diagnosed according to DSM-IV, and control subjects without history of psychiatric disorders were selected. We used SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs for the evaluation of genetic data. Of nine polymorphisms, three SNPs (rs9292101, rs1009639, and rs11956465) were associated with schizophrenia. The rs9292101 and rs11956465 showed significant associations with the risk of schizophrenia in the codominant [rs9292101, odds ratio (OR)=0.74, 95% confidence interval (CI)=0.58${\sim}$0.95, p=0.017] and recessive (rs11956465, OR=0.64, 95% CI=0.42${\sim}$0.96, p=0.034) models, respectively. The rs1009639 also was statistically related to schizophrenia in both codominant (OR=0.76, 95% CI=0.60${\sim}$0.97, p=0.025) and dominant (OR=0.66, 95% CI=0.44${\sim}$0.98, p=0.035) models. Two linkage disequilibrium (LD) blocks were made. In the analysis of haplotypes, a haplotype (GCT) in block 1 and a haplotype (CCACAG) in block 2 showed significant associations between schizophrenia and control groups (haplotype GCT, frequency=0.509, chi square=4.199, p=0.040; haplotype CCACAG, frequency=0.289, chi square=5.691, p=0.017). The results suggest that IL31RA may be associated with risk of schizophrenia in Korean population.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9177-9183
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• 2014

Polymorphisms of inflammation-related genes have been found to be associated with non-Hodgkin lymphoma (NHL) or some of its subtypes, but only a few relevant data have been reported in China. In this study, the Snapshot method was used to assess genetic variation; a total of 14 single nucleotide polymorphisms (SNPs) for 6 inflammatory factors in 157 NHL cases (64 Uygur ethnic subjects, 93 Han Chinese) and 435 controls (231 Uygur and 204 Han Chinese) were studied from the Xinjiang province of China. Haplotype distribution was estimated using PHASE 2.3 software. Statistical differences in the genotype and haplotype frequencies between case and control groups were also considered and estimated. For the Han population, the geneotype distributions for TNF-${\alpha}rs1800629$, TNF-${\alpha}rs1800630$, IL-6 rs1800795, IL-6 rs1800797, NF-KB1 rs1585215 and TLR-4 rs4986790 showed significant differences between the case and control groups (p<0.05). The TNF-${\alpha}$ gene frequencies of ACG and CCA haplotypes in the cases were higher than in the controls (OR=2.45, 95% CI: 1.55-3.89, p=0.0002, OR=2.53, 95% CI: 1.10-5.80, p=0.029, respectively), and the same findings were detected for TNF-${\beta}$ gene CA haplotype (OR=1.87, 95% CI: 1.21-2.90, p=0.0054). However, for the Uygur population, no such significant differences were detected within the gene-type distribution of the 14 SNPs. The TNF-${\alpha}$ gene frequency of the CCA haplotype between the two groups (OR=1.98, 95% CI: 1.11-3.51, p=0.021) revealed a statistically significant difference. Our results showed that polymorphic variations of inflammation-related genes could be important to the NHL etiology of the Han population, and that these may only have limited influence on the Uygur population.

• Clinical and Experimental Pediatrics
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• v.51 no.9
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• pp.1007-1011
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• 2008

Purpose : Febrile seizure (FS) is the most common type of seizure. The role of genetic factors in FSs has long been recognized. A positive family history can be elicited in 25-40% of patients with FSs; nonetheless, the genes responsible for FSs in the majority of the population remain unknown. Interleukin-$1{\beta}$ ($IL-1{\beta}$) is a pro-inflammatory cytokine that acts as an endogenous pyrogen. Thus, $IL-1{\beta}$ could be involved in the pathophysiology of FSs. Methods : To determine whether or not single nucleotide polymorphisms of the $IL-1{\beta}$ gene are associated with susceptibility to simple FSs, $IL-1{\beta}$ promoter -31 and -511 genotyping was performed by means of polymerase chain reaction-restriction fragment (PCR-RF) length polymorphism in 40 FS patients (20 sporadic and 20 familial FS patients) and 33 controls. Results : There were no significant differences in the frequencies of -31 C/T and -511 C/T in the $IL-1{\beta}$ promoter gene, between simple FS patients and controls. Conclusion : The frequency of CT/CT increased relatively in familial FS patients. A study examining a larger number of FS patients is needed.

• Korean Journal of Biological Psychiatry
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• v.20 no.3
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• pp.91-96
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• 2013

Objectives The aim of this study is to evaluate the association between rs6280 and rs905568 genetic polymorphism of DRD3 gene and the treatment response of amisulpride. Methods After six weeks treatment of amisulpride, 125 schizophrenia patients were interviewed based on the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression-Severity (CGI-S). The genotyping for rs6280 and rs905568 was performed using TaqMan single nucleotide polymorphism (SNP) genotyping assay. Results There was no significant difference in the frequency of genotype and allele of rs6280 between the responders and non-responders based on the total, positive, and general score of PANSS and CGI-S score. However, there was a significant association between this SNP and treatment response in the negative score of PANSS (${\chi}^2=5.23$, p = 0.022). There was no significant association between rs905568 and the response in positive, negative, general, and total PANSS score and CGI-S score. Conclusions This is the first positive association study between DRD3 gene and the treatment response of negative symptoms to amisulpride in Korean schizophrenia patients. A larger scale research on more SNP of the DRD3 gene will make a progress in the study of pharmacogenetics on the treatment response of the amisulpride.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4301-4306
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• 2013

Aim: Apoptosis has been considered as a fundamental component in cancer pathogenesis, and related genetic factors might play an important role in gastric cardiac adenocarcinoma (GCA) genesis. Methods: We conducted a hospital based case.control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): BCL2 rs17757541 C>G, BCL2 rs12454712 T>C, FAS rs2234767 G>A, FASL/FASLG rs763110 C>T, ERBB2 rs1136201 A>G and VEGFR2/KDR rs11941492 C>T on the development of GCA. A total of 243 GCA cases and 476 controls were recruited for the study and genotypes were determined using a custom-by-design 48-Plex SNPscan$^{TM}$ Kit. Results: The BCL2 rs17757541 C>G polymorphism was associated with increased risk of GCA. However, there was no significant associations with the other five SNPs. Stratified analyses indicated a significantly increased risk of GCA associated with the BCL2 rs17757541 C>G polymorphism among males, older patients and those with a history of smoking or drinking. Conclusion: These findings indicated that the functional polymorphism BCL2 rs17757541 C>G might contribute to GCA susceptibility. However, our results were limited by small sample size. Future larger studies are required to confirm our current findings.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.8
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• pp.1089-1095
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• 2012

Neonatal Fc receptor (FcRn) gene encodes a receptor that binds the Fc region of monomeric immunoglobulin G (IgG) and is responsible for IgG transport and stabilization. In this report, the 8,900 bp porcine FcRn genomic DNA structure was identified and putative FcRn protein included 356 amino acids. Alignment and phylogenetic analysis of the porcine FcRn amino acid sequences with their homologies of other species showed high identity. Tissues expression of FcRn mRNA was detected by real time quantitative polymerase chain reaction (Q-PCR), the results revealed FcRn expressed widely in ten analyzed tissues. One single nucleotide polymorphism (SNP) (HQ026019:g.8526 C>T) in exon6 region of porcine FcRn gene was demonstrated by DNA sequencing analysis. A further analysis of SNP genotypes associated with serum Classical Swine Fever Virus antibody (anti-CSFV) concentration was performed in three pig populations including Large White, Landrace and Songliao Black pig (a Chinese indigenous breed). Our results of statistical analysis showed that the SNP had a highly significant association with the level of anti-CSFV antibody (At d 20; At d 35) in serum (p = 0.008; p = 0.0001). Investigation of expression and polymorphisms of the porcine FcRn gene will help us in further understanding the molecular basis of the antibody regulation pathway in the porcine immune response. All these results indicate that FcRn gene might be regarded as a molecular marker for genetic selection of anti-CSFV antibody level in pig disease resistance breeding programmes.