Genome-Wide Association Study ; Genotype ; Humans ; Molecular Epidemiology ; methods

Biomarkers are characteristic biological properties that can be detected and measured in a variety of biological matrices in the human body, including the blood and tissue, to give an indication of whether there is a threat of disease, if a disease already exists, or how such a disease may develop in an individual case. Along the continuum from exposure to clinical disease and progression, exposure, internal dose, biologically effective dose, early biological effect, altered structure and/or function, clinical disease, and disease progression can potentially be observed and quantified using biomarkers. While the traditional discovery of biomarkers has been a slow process, the advent of molecular and genomic medicine has resulted in explosive growth in the discovery of new biomarkers. In this review, issues in evaluating biomarkers will be discussed and the biomarkers of environmental exposure, early biologic effect, and susceptibility identified and validated in epidemiological studies will be summarized. The spectrum of genomic approaches currently used to identify and apply biomarkers and strategies to validate genomic biomarkers will also be discussed.
Disease Progression ; Environmental Exposure ; *Epidemiologic Studies ; *Genetic Markers ; Humans ; Molecular Epidemiology/*methods ; Neoplasms/epidemiology ; Republic of Korea/epidemiology

Mendelian randomization (MR) in epidemiology is the use of genetic variants as instrumental variables (IVs) in non-experimental design to make causality of a modifiable exposure on an outcome or disease. It assesses the causal effect between risk factor and a clinical outcome. The main reason to approach MR is to avoid the problem of residual confounding. There is no association between the genotype of early pregnancy and the disease, and the genotype of an individual cannot be changed. For this reason, it results with randomly assigned case-control studies can be set by regressing the measurements. IVs in MR are used genetic variants for estimating the causality. Usually an outcome is a disease and an exposure is risk factor, intermediate phenotype which may be a biomarker. The choice of the genetic variable as IV (Z) is essential to a successful in MR analysis. MR is named ‘Mendelian deconfounding’ as it gives to estimate of the causality free from biases due to confounding (C). To estimate unbiased estimation of the causality of the exposure (X) on the clinically relevant outcome (Y), Z has the 3 core assumptions (A1-A3). A1) Z is independent of C; A2) Z is associated with X; and A3) Z is independent of Y given X and C; The purpose of this review provides an overview of the MR analysis and is to explain that using an IV is proposed as an alternative statistical method to estimate causal effect of exposure and outcome under controlling for a confounder.
Bias (Epidemiology) ; Case-Control Studies ; Epidemiology ; Genotype ; Mendelian Randomization Analysis ; Methods ; Molecular Epidemiology ; Phenotype ; Pregnancy ; Random Allocation ; Risk Factors

OBJECTIVETo assess the application of IS6110-restriction fragment length polymorphism (RFLP), Spoligotyping and mycobacterial interspersed repetitive unit (MIRU) in epidemiological studies of tuberculosis and to discuss the characteristics of Mycobacterium tuberculosis strains in different regions in China.

METHODSMycobacterium tuberculosis strains, with a total number of 158 isolates, were subjected to IS6110-RFLP, Spoligotyping and MIRU.

RESULTSThe numbers of patterns produced by IS6110-RFLP, Spoligotyping, and MIRU typing were 118, 20 and 105 respectively. The discriminatory power of IS6110-RFLP was higher than that of Spoligotyping. However, when the copies of IS6110 were lower than 10, the discriminatory power of Spoligotyping improved obviously. The discriminatory power of MIRU typing was close to that of IS6110-RFLP for typing of Mycobacterium tuberculosis. In MIRU loci, there were four loci (loci 4, 10, 26, 40) with higher diversity. Significant differences among the Mycobacterium tuberculosis between Guangdong and other regions in clustered rate and the proportion of Beijing genotype (P < 0.05) were found. The clustered rates and the proportion of Beijing genotype in Guangdong were lower than that in other regions.

CONCLUSIONThe results of this study indicated that either IS6110-RFLP, Spoligotyping or MIRU technique was useful for epidemiological studies on tuberculosis in China and the strains in different regions had different characterishes in China.

China ; epidemiology ; DNA Fingerprinting ; methods ; DNA, Bacterial ; genetics ; Humans ; Molecular Epidemiology ; Mycobacterium tuberculosis ; classification ; genetics ; isolation & purification ; Polymerase Chain Reaction ; methods ; Polymorphism, Restriction Fragment Length ; Tuberculosis ; epidemiology ; microbiology

BACKGROUND: Enterococci have emerged in recent years as a frequent cause of life-threatening nosocomial infections. The emergence of vancomycin-resistant enterococci(VRE) presents as an increasingly important problem particularly in the treatment and the potential dissemination of vancomycin-resistance. The purpose of this study is to determine the phenotypes and genotypes of VRE isolated from five hospitals and to study the genetic relatedness among them. METHODS: Antimicrobial susceptibility patterns and amplification of vancomycin resistance genes were used for phenotyping and genotyping of 42 VRE isolates respectively. For 21 isolates with vanA or vanB gene, plasmid profiles and pulsed field gel electrophoresis(PFGE) patterns were analyzed for molecular epidemiologic study. RESULTS: Out of 42 isolates, 21 were identified as E. faecium, 6 as E. faecalis, 2 as E. avium, and 13 as E. casseliflavus. Phenotyping showed 14 isolates as VanA(33%), 7 as VanB(17%) and 21 as VanC(50 %). Genotyping resulted in 12 isolates as vanA(5 of E. faecalis and 7 of E. faecium) and 9 as vanB(all E. faecium). Genotyping results were concordant with phenotyping results except for the two E. faecium isolates of VanA which had vanB genotype. Intrahospital spread of the same strains was proven in three hospitals by plasmid profiles and PFGE analysis. CONCLUSION: The study demonstrated a considerable number of VRE isolates in Korea and intrahospital spread proven by molecular epidemiologic methods. Although VRE infection has been considered very rare in Korea, practical guidelines including restriction of vancomycin usage and surveillance, are warranted to prevent infection and dissemination of VRE.
Cross Infection ; Epidemiologic Methods ; Epidemiologic Studies ; Genotype ; Korea* ; Molecular Epidemiology* ; Phenotype ; Plasmids ; Vancomycin ; Vancomycin Resistance

China ; Genotype ; Measles virus ; genetics ; isolation & purification ; Molecular Epidemiology ; methods ; Nucleoproteins ; genetics ; Polymerase Chain Reaction

Animals ; Environmental Microbiology ; Humans ; Malaysia ; Molecular Typing ; methods ; Salmonella Infections ; epidemiology ; microbiology ; Salmonella enterica ; classification ; genetics

Animals ; Genotype ; Humans ; Leptospira interrogans ; classification ; genetics ; Minisatellite Repeats ; genetics ; Molecular Epidemiology ; methods

BACKGROUND: It has proven challenging to investigate the molecular epidemiology of Mycobacterium leprae, the causative agent of leprosy, due to difficulties with culturing of the organism and a lack of genetic heterogeneity between strains. Recently, A panel of variable-number tandem-repeat (VNTR) markers and an alternative method, structure-neighbor clustering, which assigns isolates with the most similar genotypes to the same groups and, subsequently, subgroups, without inferring how the strains descended from a common ancestor have been developed. METHODS: A total of 29 samples from Korea found cases were studied by 14 VTRN typing and an alternative method, structure-neighbor clustering with 13 and 14 VNTRs by Structure Program(k=10). RESULTS: Only 286 cases of 522 total cases(including database of Bellingham Research Institute) showed p>0.8(in 13 and 14 VNTRs). Almost Korea found cases(18 cases) were included in group 3(13 VNTRs), in group 9(14 VNTRs)(by Structure Program, k=10). CONCLUSIONS: The structure-neighbor clustering by Structure Program with panels of VNTR is a useful approach for investigating the molecular epidemiology of Mycobacterium leprae.
Cluster Analysis ; Genetic Heterogeneity ; Genotype ; Korea ; Leprosy ; Methods ; Molecular Epidemiology ; Mycobacterium leprae ; Mycobacterium

BACKGROUND: Stenotrophomonas maltophilia is one of several opportunistic pathogens of growing significance. Several studies on the molecular epidemiology of S. maltophilia have shown clinical isolates to be genetically diverse. MATERIALS AND METHODS: A total of 121 clinical isolates tentatively identified as S. malophilia from seven tertiary-care hospitals in Korea from 2007 to 2011 were included. Species and groups were identified using partial gyrB gene sequences and antimicrobial susceptibility testing was performed using a broth microdilution method. Multi locus variable number of tandem repeat analysis (MLVA) surveys are used for subtyping. RESULTS: Based on partial gyrB gene sequences, 118 isolates were identified as belonging to the S. maltophilia complex. For all S. maltophilia isolates, the resistance rates to trimethoprime-sulfamethoxazole (TMP/SMX) and levofloxacin were the highest (both, 30.5%). Resistance rate to ceftazidime was 28.0%. 11.0% and 11.9% of 118 S. maltophilia isolates displayed resistance to piperacillin/tazobactam and tigecycline, respectively. Clade 1 and Clade 2 were definitely distinguished from the data of MLVA with amplification of loci. All 118 isolates were classified into several clusters as its identification. CONCLUSION: Because of high resistance rates to TMP/SMX and levofloxacin, the clinical laboratory department should consider providing the data about other antimicrobial agents and treatment of S. maltophilia infections with a combination of antimicrobials can be considered in the current practice. The MLVA evaluated in this study provides a fast, portable, relatively low cost genotyping method that can be employed in genotypic linkage or transmission networks comparing to analysis of the gyrB gene.
Anti-Infective Agents ; Ceftazidime ; Korea ; Levofloxacin ; Methods ; Molecular Epidemiology ; Stenotrophomonas maltophilia* ; Stenotrophomonas* ; Tandem Repeat Sequences*