• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3165-3172
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• 2012

Objective: Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to summarize the evidence for associations. Methods: Studies focusing on the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Results: According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646 healthy controls, were included in the meta-analysis. The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97, P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94, P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively). Conclusion: This meta-analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840 in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors.

• Genomics & Informatics
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• 제12권3호
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• pp.114-120
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• 2014

Bone mineral density (BMD) is one of the quantitative traits that are genetically inherited and affected by various factors. Over the past years, genome-wide association studies (GWASs) have searched for many genetic loci that influence BMD. A recent meta-analysis of 17 GWASs for BMD of the femoral neck and lumbar spine is the largest GWAS for BMD to date and offers 64 single-nucleotide polymorphisms (SNPs) in 56 associated loci. We investigated these BMD loci in a Korean population called Korea Association REsource (KARE) to identify their validity in an independent study. The KARE population contains genotypes from 8,842 individuals, and their BMD levels were measured at the distal radius (BMD-RT) and midshaft tibia (BMD-TT). Thirteen genomic loci among 56 loci were significantly associated with BMD variations, and 3 loci were involved in known biological pathways related to BMD. In order to find putative functional variants, nearby SNPs in relation to linkage equilibrium were annotated, and their possible functional effects were predicted. These findings reveal that tens of variants, not a single factor, may contribute to the genetic architecture of BMD; have an important role regardless of ethnic group; and may highlight the importance of a replication study in GWASs to validate genuine loci for BMD variation.

• Tuberculosis and Respiratory Diseases
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• 제76권3호
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• pp.105-113
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• 2014

From January 2012 up until March 2013, many articles with huge clinical importance in asthma were published based on large numbered clinical trials or meta-analysis. The main subjects of these studies were the new therapeutic plan based on the asthma phenotype or efficacy along with the safety issues regarding the current treatment guidelines. For efficacy and safety issues, inhaled corticosteroid tapering strategy or continued long-acting beta agonists use was the major concern. As new therapeutic trials, monoclonal antibodies or macrolide antibiotics based on inflammatory phenotypes have been under investigation, with promising preliminary results. There were other issues on the disease susceptibility or genetic background of asthma, particularly for the "severe asthma" phenotype. In the era of genome and pharmacogenetics, there have been extensive studies to identify susceptible candidate genes based on the results of genome wide association studies (GWAS). However, for severe asthma, which is where most of the mortality or medical costs develop, it is very unclear. Moreover, there have been some efforts to find important genetic information in order to predict the possible disease progression, but with few significant results up until now. In conclusion, there are new on-going aspects in the phenotypic classification of asthma and therapeutic strategy according to the phenotypic variations. With more pharmacogenomic information and clear identification of the "severe asthma" group even before disease progression from GWAS data, more adequate and individualized therapeutic strategy could be realized in the future.

• Journal of Genetic Medicine
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• 제14권1호
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• pp.8-17
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• 2017

Purpose: Pulse wave velocity (PWV) is an indicator of arterial stiffness, and is considered a marker of vascular damage. However, a genome-wide association study analyzing single nucleotide polymorphisms (SNPs) associated with brachial-ankle PWV (baPWV) has not been conducted in healthy populations. We performed this study to identify SNPs associated with baPWV in healthy populations in Korea. Materials and Methods: Genomic SNPs data for 2,407 individuals from three sites were analyzed as part of the Korean Genomic Epidemiologic Study. Without replication samples, we performed multivariable analysis as a post hoc analysis to verify the findings in site adjusted analysis. Healthy subjects aged between 40 and 70 years without self-reported history or diagnosis of hypertension, diabetes, hyperlipidemia, heart disease, cerebrovascular disease and cancer were included. We excluded subjects with a creatinine level >1.4 mg/dL (men) and 1.2 mg/dL (women). Results: In the site-adjusted association analysis, significant associations (P<$5{\times}10^{-8}$) with baPWV were detected for only 5 SNPs with low minor allele frequency. In multivariable analysis adjusted by age, sex, height, body mass index, mean arterial pressure, site, smoking, alcohol, and exercise, 11 SNPs were found to be associated (P<$5{\times}10^{-8}$) with baPWV. The 5 SNPs (P<$5{\times}10^{-8}$) linked to three genes (OPCML, PRR35 and RAB40C) were common between site-adjusted analysis and multivariable analysis. However, meta-analysis of the result from three sites for the 11 SNPs showed no significant associations. Conclusion: Using the recent standard for genome-wide association study, we did not find any evidence of significant association signals with baPWV.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8051-8055
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• 2014

Background: A common genetic variant rs3757318, located in intron of C6orf97, was firstly identified to be associated with breast cancer (BC) risk by a genome-wide association (GWA) study. However, subsequent validation studies with different ethnicities have yielded conflicting results. Materials and Methods: We performed a meta-analysis to synthesize all available data for evaluating the precise effect of this variant on BC susceptibility. Results: A total of 8 articles containing 11 studies with 62,891 cases and 65,635 controls were included in this meta-analysis. When compared to the G allele, the rs3757318-A allele was significantly associated with BC risk with the pooled OR of 1.21 (95% CI=1.15 - 1.29, P<0.001) but with obvious between-study heterogeneity (P=0.040). Stratified analysis suggested that diversity of ethnicity along with control source may explain part of the heterogeneity. Similarly, significant associations were also identified in heterozygote, homozygote, dominant and recessive genetic models. Sensitivity and publication bias analyses indicated robust stability of our results. Conclusions: Our present meta-analysis demonstrated that the variant rs3757318 is associated with increased BC risk. Nevertheless, further studies are needed to clarify the underlying biological mechanisms.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4417-4422
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• 2014

ERCC2 is an essential component of the nucleotide excision repair pathway which is involved in the effective maintenance of genome integrity. Association studies on ERCC2 polymorphisms and glioma risk have yielded inconclusive results. This meta-analysis was performed to gain a better insight into the relationship between ERCC2 polymorphisms and glioma risk. A systematic literature search updated to December 2, 2013 was performed in the Pubmed and EMBASE databases. Crude pooled odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were used to estimate the association between ERCC2 polymorphisms and glioma risk under a suitable effect model according to heterogeneity. All analyses were performed using Review Manager 5 (version 5.2) and STATA (version 12.0). The combined results demonstrated rs13181 to be significantly associated with glioma risk (G allele versus T allele: OR=1.15, 95% CI=1.05-1.26, P=0.002; dominant model: OR=1.22, 95% CI=1.07-1.39, P=0.002; recessive model: OR=1.18, 95% CI=0.98-1.41, P=0.070). We also found that rs13181 acts in an allele dose-dependent manner (GG versus TT: OR=1.30, 95% CI=1.07-1.57, P=0.009; TG versus TT: OR=1.20, 95%=CI 1.05-1.37, P=0.009; trend test, P=0.004). However, no evidence was found in analyses for the association between other 3 ERCC2 polymorphisms (rs238406, rs1799793, and rs1052555) and susceptibility to glioma development. Our meta-analysis suggests that rs13181 is significantly associated with glioma risk in an allele dose-dependent manner, whereas, 3 other ERCC2 polymorphisms (rs238406, rs1799793, and rs1052555) may have no influence.

• Tuberculosis and Respiratory Diseases
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• 제77권4호
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• pp.161-166
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• 2014

Since tuberculosis (TB) remains a major global health concern and the incidence of multi-drug resistant (MDR)-TB is increasing globally, new modalities for the detection of TB and drug resistant TB are needed to improve TB control. The Xpert MTB/RIF test can be a valuable new tool for early detection of TB and rifampicin resistance, with a high sensitivity and specificity. Late-generation fluoroquinolones, levofloxacin, and moxifloxacin, which are the principal drugs for the treatment of MDR-TB, show equally high efficacy and safety. Systemic steroids may reduce the overall TB mortality attributable to all forms of TB across all organ systems, although inhaled corticosteroids can increase the risk of TB development. Although fixed dose combinations were expected to reduce the risk of drug resistance and increase drug compliance, a recent meta-analysis found that they might actually increase the risk of relapse and treatment failure. Regarding treatment duration, patients with cavitation and culture positivity at 2 months of TB treatment may require more than 6 months of standard treatment. New anti-TB drugs, such as linezolid, bedaquiline, and delamanid, could improve the outcomes in drug-resistant TB. Nontuberculous mycobacterial lung disease has typical clinical and immunological phenotypes. Mycobacterial genotyping may predict disease progression, and whole genome sequencing may reveal the transmission of Mycobacterium abscessus. In refractory Mycobacterium avium complex lung disease, a moxifloxacin-containing regimen was expected to improve the treatment outcome.

• 한국산학기술학회:학술대회논문집
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• 한국산학기술학회 2003년도 Proceeding
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• pp.57-64
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• 2003

Achieving the beneficiary goal of recent discovery in human genome project still needs a way to retrieve and analyze the exponentially expanding bio-related information. Research on bio-related fields naturally applies knowledge discovered to the current problem and make inferences to extract new information where shared concepts and data containing information need to be defined and used in a coherent way. In such a professional domain, while the need to help users reduce their work and to improve search results has been emerged. methods for systematic retrieval and adequate exchange of relevant information are still in their infancy. The design of our system aims at improving the quality of information retrieval in a professional domain by utilizing both corpus-based and concept-based ontology. Meta-rules of helping users to make an adequate query are formed into an ontology in the domain. The integration of those knowledge permits the system to retrieve relevant information in a more semantic and systematic fashion. This work mainly describes the query models with details of GUI and a secondary query generation of the system.

• BMB Reports
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• 제55권11호
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• pp.553-558
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• 2022

Hepatocellular carcinoma (HCC) is dangerous cancer that often evades early detection because it is asymptomatic and an effective detection method is lacking. For people with chronic liver inflammation who are at high risk of developing HCC, a sensitive detection method for HCC is needed. In a meta-analysis of The Cancer Genome Atlas pan-cancer methylation database, we identified a CpG island in the USP44 promoter that is methylated specifically in HCC. We developed methylation-sensitive high-resolution melting (MS-HRM) analysis to measure the methylation levels of the USP promoter in cell-free DNA isolated from patients. Our MS-HRM assay correctly identified 40% of patients with early-stage HCC, whereas the α-fetoprotein test, which is currently used to detect HCC, correctly identified only 25% of early-stage HCC patients. These results demonstrate that USP44 MS-HRM analysis is suitable for HCC surveillance.

• Genomics & Informatics
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• 제21권4호
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• pp.49.1-49.11
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• 2023

Recent advances in sequencing technologies and platforms have enabled to generate metagenomics sequences using different sequencing platforms. In this study, we analyzed and compared shotgun metagenomic sequences generated by HiSeq3000 and BGISEQ-500 platforms from 12 sediment samples collected across the Norwegian coast. Metagenomics DNA sequences were normalized to an equal number of bases for both platforms and further evaluated by using different taxonomic classifiers, reference databases, and assemblers. Normalized BGISEQ-500 sequences retained more reads and base counts after preprocessing, while a slightly higher fraction of HiSeq3000 sequences were taxonomically classified. Kaiju classified a higher percentage of reads relative to Kraken2 for both platforms, and comparison of reference database for taxonomic classification showed that MAR database outperformed RefSeq. Assembly using MEGAHIT produced longer assemblies and higher total contigs count in majority of HiSeq3000 samples than using metaSPAdes, but the assembly statistics notably improved with unprocessed or normalized reads. Our results indicate that both platforms perform comparably in terms of the percentage of taxonomically classified reads and assembled contig statistics for metagenomics samples. This study provides valuable insights for researchers in selecting an appropriate sequencing platform and bioinformatics pipeline for their metagenomics studies.