• Journal of Korean Neurosurgical Society
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• 제49권1호
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• pp.8-12
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• 2011

Objective: Ossification of the posterior longitudinal ligament (OPLL) has a strong genetic component. Specific gene polymorphisms may be associated with OPLL in several genes which regulate calcification in chondrocytes, change of extracellular collagen matrix and secretions of many growth factors and cytokines controlling bone morphogenesis. Toll-like receptor 5 (TLR5) may playa role in the pathogenesis of OPLL by intermediate nuclear factor-kappa B (NF-${\kappa}B$). The current study focused on coding single nucleotide polymorphisms (SNPs) of TLR5 for a case-control study investigating the relationship between TLR5 and OPLL in a Korean population. Methods: A total of 166 patients with OPLL and 231 controls were recruited for a case-control association study investigating the relationship between SNPs of TLR5 gene and OPLL. Four SNPs were genotyped by direct sequencing (rs5744168, rs5744169, rs2072493, and rs5744174). SNP data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. Multiple logistic regression analysis with adjustment for age and gender was performed to calculate an odds ratio (OR). Results: None of SNPs were associated with OPLL in three alternative models (codominant, dominant, and recessive models; p> 0.05). A strong linkage disequilibrium block, including all 4 SNPs, was constructed using the Gabriel method. No haplotype was significantly associated with OPLL in three alternative models. Conclusion: These results suggest that Toll-like receptor 5 gene may not be associated with ossification of the posterior longitudinal ligament risk in Korean population.

• Asian-Australasian Journal of Animal Sciences
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• 제20권5호
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• pp.653-660
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• 2007

In this study, we have investigated sequence variants in the PRNP gene of 20 individuals belonging to the Korean cattle, and have analyzed and compared genetic features between varieties of other cattle breeds. Of the 73 sequence variants identified in Korean cattle, 27 were identified for the first time in this study, whereas 46 of these polymorphisms had previously been isolated. We discovered a 2.6 kb SNP hot spot region localized on the putative promoter region of the PRNP gene. Furthermore, the copy numbers of the octapeptide repeat (24 bp indel) which is detected on the coding sequence (CDS) of the PRNP exhibited a completely homozygous 6/6 genotype which is dominant in other cattle breeds. We also characterized a new 19 bp/10 bp allele located on the putative promoter region of the PRNP gene, which represented 0.71 in allele frequency. To the best of our knowledge, this report is the first to address polymorphisms of the PRNP gene structure in Korean cattle in which BSE has yet to be discovered. Therefore, our findings may prove useful with regard to our current understanding of allelic diversity in bovine species, and may also provide new insights into the genetic factors associated with susceptibility or resistance to BSE.

• Journal of Korean Neurosurgical Society
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• 제63권5호
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• pp.559-565
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• 2020

Objective : Conflicting results regarding SOX17 genes and the risk of intracranial aneurysms (IA) exist in the Korean population, although significant positive correlations were noted in genome-wide association studies in European and Japanese populations. Therefore, we aimed to investigate an association between SOX17 gene variants and IA using exome sequencing data. Methods : This study included 26 age-gender matched IA patients and 26 control subjects. The SOX17 gene variants identified from whole-exome sequencing data were examined. Genetic associations to estimate odds ratio (OR) and 95% confidence interval (CI) were performed using the software EPACTS. Results : The mean age of the IA and control groups were 51.0±9.3 years and 49.4±14.3 years, respectively (p=0.623). Seven variants of SOX17, including six single nucleotide polymorphisms and one insertion and deletion, were observed. Among these variants, rs12544958 (A>G) showed the most association with IA, but the association was not statistically significant (OR, 1.97; 95% CI, 0.81-4.74; p=0.125). Minor allele frequencies of the IA patients and controls were 0.788 and 0.653, respectively. None of the remaining variants were significantly associated with IA formation. Conclusion : No significant association between SOX17 gene variants and IA were noted in the Korean population. A large-scale exome sequencing study is necessary to investigate any Korean-specific genetic susceptibility to IA.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9241-9247
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• 2014

Background: Rs31489 in the cleft lip and palate transmembrane1-like gene (CLPTM1L) has been identified to be associated with lung cancer through genome-wide association studies (GWAS). However, some recent replication studies yielded inconclusive results. Thus, we undertook this study to investigate the precise effect of rs31489 on lung cancer susceptibility. Materials and Methods: A hospital-based case-control study in 1,673 Chinese subjects (611 individuals with lung cancer and 1,062 controls) and a meta-analysis among 32,199 subjects (16,364 cases and 15,835 controls) were performed in this study. Results: In our case-control study, rs31489 was inversely associated with lung cancer (AC versus CC: OR=0.68, 95%CI=0.52-0.88; additive model: OR=0.68, 95%CI=0.54-0.85; dominant model: OR=0.65, 95%CI =0.51-0.84). Stratification analysis by smoking status showed a significant association and strong genetic effect in non-smokers but not in smokers. Our meta-analysis further confirmed the association, although with significant heterogeneity contributed by study design and source of controls, as shown by stratified analysis. Sensitive and cumulative analyses both indicated robust stability of our results. In addition, there was no observable publication bias in our meta-analysis. Conclusions: Overall, the findings from our replication study and meta-analysis demonstrated that CLPTM1L gene rs31489 is significantly associated with lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.21-25
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• 2013

Background: Genetic factors and environmental factors play a role in pathogenesis of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the association of folate intake and Methylenetetrahydrofolate reductase C677T polymorphism with ESCC was conflicting. We conducted a meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk. Methods: MEDLINE, EMBASE and the Chinese Biomedical Database were searched in our study. The quality of studies were evaluated by predefined scale, and The association of polymorphisms of MTHFR C677T and folate intake and ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs). Results: 19 studies (4239 cases and 5575 controls) were included for meta-analysis. A significant association was seen between individuals with MTHFR 677 CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC risk (p<0.05). Low intake of folate had significantly higher risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high intake of folate did not find significant high risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. Conclusions: Our meta-analysis indicated the folate intake and MTHFR 677CT/TT are associated with the risk of ESCC, and folate showed a significant interaction with polymorphism of MTHFR C677T.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3855-3859
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• 2016

Colorectal cancer (CRC) is reproted to be the third most common cancer worldwide and the fourth most common cause of cancer related deaths. CRC is considered to be a multifactorial disease whose risk varies due to the complex interaction between individual genetic basis and disposure to multiple endogenous factors. Glutathione S-transferases are pro-carcinogenic in CRC and are required for the conjugation between chemotherapeutics and broad spectrum xenobiotics. One hundred and eleven patients with CRC and 128 control subjects without any cancer history were enrolled in this study. Multiplex PCR was applied to determine polymorphisms for the GSTT1 and M1 genes, and PCR-RFLP was applied for the GSTP1 (Ile105Val) gene polymorphism. Values p<0.05 were defined as statistically significant. We detected a significant high correlation between predisposition for CRC and presence of the Ile/Ile genotype of the GSTP1 (IIe105Val) gene polymorphism, but we did not find a significant relationship between predisposition for CRC and GSTT1 and M1 deletion polymorphisms. In addition, we did not determine a relationship between GSTT1, M1 and P1 gene polymorphisms and any clinicopathological features of CRC. GSTT1 null/GSTM1 positive and GSTT1 null/GSTM1 positive/GSTP1 Ile/Ile genotypes were significantly higher in the patient group. Our results revealed that there is no relationship among CRC, its clinicopathologic features, and GSTT1 M1 gene polymorphisms. However, there was a significant correlation between CRC and the GSTP1 Ile/Ile genotype. Further studies with larger patient groups are required to delineate the relationships between GST gene polymorphisms and the clinicopathologic features of CRC in Turkey.

• Journal of Yeungnam Medical Science
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• 제17권2호
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• pp.108-122
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• 2000

Background: Models of attention deficit hyperactivity disorder(ADHD) that have proposed a hypodopaminergic state resulting in hypofunction of the prefrontal circuitry have assumed a unitary dopamine system, which largely ignores the distinct functional differences between mesocortical dopamine system and nigrostriatal dopamine system. Purpose: The author's goal was to develop a pathophysiological model for ADHD with greater explanotory power than dopaminergic hypofunction hypothesis in prefronal circuitry. Material and Methods: Published clinical findings on ADHD were integrated with data from genetic, pharmacological, neuroimaging studies in human and animals. Results: Molecular genetic studies suggest that three genes may increase the susceptibility to ADHD. The three candidate genes associated with ADHD are each involved in dopaminergic function, and this consistent with the neurobiologic studies implicating catecholamines in the etiology of ADHD. Pharmacological data also provide compelling support for dopamine and noradrenergic hypothesis of ADHD. Neuroimaging studies lend substantial support for the hypothesis that right-sided abnormalities of prefrontal-basal ganglia circuit would be found in ADHD. Conclusions: The present hypothesis takes advantage of the major differences between the two pertinent dopamine systems. Mesocortical dopamine system, which largely lacks inhibitory autoreceptors, is ideally positioned to regulate cortical inputs, thus improving the signal-to-noise ratio for biologically valued signals. In this circuit, therapeutic doses of stimulants are hypothesized to increase postsynaptic dopamine effects and enhance executive functions. By contrast, symptoms of hyperactivity/impulsivity in ADHD are hypothesized to be associated with relative overactivity of nigrostriatal circuit. This nigrostriatal circuit is tightly regulated by inhibitory autoreceptoors as well as by long distance feedback from the cortex, and slow diffusion of therapeutic doses of stimulant via oral administration is hypothesized to produce a net inhibition of dopaminergic neurotransmission and improves hyperactivity.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.953-956
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• 2016

The risk of developing cervical cancer in women infected with human papillomavirus (HPV) may be influenced by an individual's genetic susceptibility. Published data linking single nucleotide polymorphisms (SNPs) in the tumor necrosis factor-alpha (TNF-${\alpha}$) promoter region at positions -308G>A (rs1800629) and -238G>A (rs361525) to cervical cancer risk have been inconclusive. In this study, we examined 251 cervical specimens and classified them into two groups according to their cytological findings: 121 cancer cases and 130 controls (low-grade squamous intraepithelial lesion and normal cytology). All specimens were typed by PCR and sequencing for TNF-${\alpha}$ promoter -308G>A (rs1800629) and -238G>A (rs361525). The genotype distribution of SNPs in either rs1800629 or rs361525 did not significantly demonstrate higher frequency in the cancer group (p=0.621 and p=0.68, respectively). Based on these results, neither the TNF-${\alpha}$ promoter -308G>A (rs1800629) nor the -238G>A (rs361525) polymorphism presents a major risk factor for cervical cancer among Thai women. Larger studies are necessary to elucidate possible genetic mechanisms influencing cervical cancer development.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7589-7594
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• 2015

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules, implicated in several activities like initiation, progression and prognosis of various cancers. Single nucleotide polymorphisms (SNPs) in miRNA genes can lead to alteration in mRNA expression, resulting in diverse functional consequences. The aim of our study was to investigate the association of miR-149C>T and miR-196a2C>T SNPs with susceptibility to development of oral squamous cell carcinoma (OSCC) in South Indian subjects. Materials and Methods: 100 OSCC patients and 102 healthy controls from the general population were recruited for the study. Genetic analysis was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) as per a standard protocol. Results: The genotype frequencies in miR-196a2 polymorphism, of TT, CT and CC in the OSCC patients were 69%,10% and 22% respectively while for control group it was 80%, 15% and 5% respectively. The CC genotype of miR196a2 polymorphism was significantly associated with oral squamous cell carcinoma. The genotype frequencies in miR-149 polymorphisms of CC, CT and TT in the oral squamous cell carcinoma (OSCC) patients were 72%, 22% and 6% respectively and for control group 88%, 12% and 0% respectively. CT and TT genotypes of miR149 polymorphism were found to be significantly associated with OSCC (p = 0.05 and 0.07). Conclusions: Our study suggests that miR-196a2C>T and miR-149C>T polymorphisms may play crucial roles in the development of OSCC in South Indian subjects.

• Genomics & Informatics
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• 제6권2호
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• pp.77-83
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• 2008

Human leucine-rich alpha-2-glycoprotein 1 (LRG1) was first identified as a trace protein in human serum. The primary sequence of LRG1 includes repeated leucine residues and putative membrane-binding domains. But, there is no published information on the genetic variation of this gene. In this study, LRG1 was identified as one of several upregulated genes in RA patients. We examined the expression levels of LRG1 between an RA patient and a healthy control by RT-PCR and validated that LRG1 was highly expressed in RA patients compared with controls. We identified the possible variation sites and single nucleotide polymorphisms (SNPs) in the human LRG1 gene by direct sequencing and analyzed the association of genotype and allele frequencies between RA patients and a control group without RA. We further investigated the relationship between these polymorphisms and the level of RF or anti-CCP in RA patients. We identified a total of three SNPs(g.-678A>G, g.-404C>T and g.1427T>C) and two variation sites (g.-1198delA and g.-893delA) in the LRG1 gene. Our results suggest that polymorphisms of the LRG1 gene are not associated with the susceptibility of RA in the Korean population.