The aims of this study were to demonstrate the trends in seropositivity and the eradication therapy rate for Helicobacter pylori (H. pylori) over an 18-year period in an asymptomatic Korean ...population and to explore the factors associated with H. pylori seropositivity and its eradication therapy. In total, 23,770 subjects (aged 17-97 years) from a health examination center participated in this cross-sectional study from January 2016 to June 2017. Questionnaires that included questions about the participants' H. pylori eradication therapy history were collected, and anti-H. pylori IgG antibodies were measured. Among the eligible subjects, the seroprevalence of H. pylori infection was 41.5%. The H. pylori eradication therapy rate increased continuously from 2005 (13.9%) to 2011 (19.3%) and then increased again until the first half of 2017 (23.5%) (P < 0.001). After exclusion of subjects with a history of gastric surgery, gastric cancer, H. pylori eradication therapy, or gastric symptoms, H. pylori seropositivity was 43.9% in 16,885 subjects, which was significantly lower than the seropositivities in 1998 (66.9%), 2005 (59.6%), and 2011 (54.4%). The risk factors associated with H. pylori seropositivity according to multivariable analysis were male sex (odds ratio (OR) 1.34, 95% confidence interval (CI): 1.23-1.46), medium educational level (OR 1.17, 95% CI: 1.05-1.31), medium household income level (OR 1.10, 95% CI: 1.03-1.19), and age of 60-69 years (OR 8.78, 95% CI: 6.41-11.85). The observed downward trend in H. pylori seroprevalence and increase in H. pylori eradication over the 18-year period will affect upper gastrointestinal disorders in South Korea.
The method for genome-wide association study (GWAS) based on copy number variation (CNV) is not as well established as that for single nucleotide polymorphism (SNP)-GWAS. Although there are several ...tools for CNV association studies, most of them do not provide appropriate definitions of CNV regions (CNVRs), which are essential for CNV-association studies. Here we present a user-friendly program called CNVRuler for CNV-association studies. Outputs from the 10 most common CNV defining algorithms can be directly used as input files for determining the three different definitions of CNVRs. Once CNVRs are defined, CNVRuler supports four kinds of statistical association tests and options for population stratification. CNVRuler is based on the open-source programs R and Java from Sun Microsystems.
CNVRuler software is available with an online manual at the website, www.ircgp.com/CNVRuler/index.html.
The overexpression of trefoil factor family 3 (TFF3) is observed in a variety of cancers, including prostate cancer (PCa), and its potential role in carcinogenesis, such as activating the PI3K/AKT ...pathway, is suggested. However, its role and its related mechanisms in prostate tumorigenesis remain unknown. To elucidate the role of TFF3 overexpression in PCa, we silenced TFF3 in two PCa cell lines that overexpressed TFF3 and explored the molecular mechanism behind its antiapoptotic role. We also examined TFF3 expression in 108 Korean PCa specimens and 106 normal prostate tissues by immunohistochemistry (IHC) analysis. The mean TFF3 IHC score in the tumor tissues was significantly higher than that in the normal tissues (4.702 vs. 0.311, P = 2.52 × 10
). TFF3-silenced cells showed suppressed tumor cell growth and migration. TFF3 silencing decreased BCL2 and increased BAX expression. The translocation of BAX to the mitochondria was also confirmed. After TFF3 silencing, the expression of the mitochondrial proapoptotic proteins, cytochrome C and Smac/DIABLO, was elevated, and these proteins were released from the mitochondria to the cytosol. Downstream mediators of mitochondrial apoptosis, including cleaved caspase-3, caspase-9, and PARP, were also elevated. Accordingly, the proportion of apoptotic cells was significantly higher among TFF3-silenced cells. There was no difference in extrinsic apoptosis-related molecules after TFF3 silencing. All the results support that TFF3 silencing induces the downstream signaling pathway of mitochondria-mediated apoptosis. This study provides a better understanding of the mechanism of prostate tumorigenesis, suggesting TFF3 as a potential biomarker and therapeutic target of PCa.
The aim of this study was to evaluate the time trend of seropositivity of Helicobacter pylori (H. pylori) over the period of 13 years in an asymptomatic Korean population, and investigate associated ...risk factors.
This cross-sectional nationwide multicentre study surveyed anti-H. pylori IgG antibodies in 19,272 health check-up subjects (aged greater than and equal to16 years) in 2011. Risk factors for H. pylori infection were investigated using logistic regression. Seropositivity in asymptomatic subjects without H. pylori eradication was compared between the years 1998 and 2005. Birth cohort effects were also evaluated.
After exclusion of subjects with a history of H. pylori eradication therapy (n = 3,712, 19.3%) and gastric symptoms (n = 4,764, 24.7%), the seroprevalence of H. pylori infection was 54.4% in 10,796 subjects. This was significantly lower than the seroprevalence of 59.6% in 2005 and that of 66.9% in 1998, and this decrease of seropositivity of H. pylori became widespread across all ages and in most areas of the country. This decreasing trend could be explained by cohort analysis. All younger birth cohorts had a lower seroprevalence of H. pylori than older birth cohorts at the same age. Decreased seroprevalence within the same birth cohorts also accounted for this phenomenon. Clinical risk factors of H. pylori infection were higher cholesterol level (greater than and equal to 240 mg/dl) (OR = 1.33; 95% CI = 1.14-1.54), male gender, older age, low income, and residence in a rural area.
A decreasing trend of H. pylori seroprevalence due to a birth cohort effect requires further studies on its related human host factors as well as socio-economic and hygienic factors. In addition, the relationship between H. pylori infection and high cholesterol level needs more investigation regarding underlying pathogenesis.
The etiology of imperforate anus, a major phenotype of anorectal malformation (ARM), is still unknown and not a single gene has been reported to be associated with it. We studied a Korean family with ...six affected members with imperforate anus across three generations by whole exome sequencing and identified a missense mutation in the EBF2 gene (c.215C > T; p.Ala72Val). This mutation is completely segregated with the disease phenotype in the family and is evolutionarily highly conserved among diverse vertebrates. Also, this mutation was predicted to be functionally damaging. These results support that missense mutation in the EBF2 c.215C > T (p.Ala72Val) is very likely to contribute to the pathogenesis of ARM in this family.
Objective
To identify ankylosing spondylitis (AS)–associated copy number variations (CNVs) in Korean subjects and their synergistic roles in the development of AS.
Methods
A genome‐wide association ...study (GWAS) was performed in 309 patients with AS and 309 control subjects, using a copy number variant (CNV) microarray. AS‐associated CNV regions were replicated in 2 independent sets (625 patients and 891 control subjects) by quantitative polymerase chain reaction (PCR) and deletion‐typing PCR.
Results
In the CNV GWAS, 227 CNV regions were shown to be significantly associated with the risk of AS. Of the candidate CNV regions, 9 were successfully replicated in the first replication analysis: 1q32.2 (HHAT), 1p34.2 (BMP8A), 2q31.2 (PRKRA), 6p21.32 (HLA–DPB1), 11q22.1 (CNTN5), 13q13.1 (EEF1DP3), 14q24.2 (RGS6), 16p13.3, and 22q11.1 (IL17RA). The 5 deletion‐type CNV regions, in 1q32.2, 2q31.2, 6p21.32, 13q13.1, and 16p13.3, were associated with an increased risk of AS, and the other 4 CNV regions were protective. In the second replication analysis, 4 CNV regions in 1q32.2, 2q31.2, 6p21.32, and 16p13.3 were replicated. Among patients with CNV regions in ≥4 risk‐increasing loci, the risk was 18.0 times higher than that in patients without any deletions (odds ratio OR 17.98, P = 2.3 × 10−7). Among patients with CNV regions in ≥2 protective loci, the risk was 5.2 times lower than that in those without any deletions (OR 0.19, P = 4.0 × 10−10). The additive effects of simultaneous events were shown to be dependent on the frequency of CNV regions. Through deletion‐typing PCR and sequencing, the exact sizes and breakpoint sequences were defined in 4 CNV regions. The mechanism of all 3 deletions was shown to be microhomology‐based nonhomologous end joining.
Conclusion
The results of this study can help to identify pathogenic mechanisms of AS and can easily be applied in the development of algorithms estimating the risk of AS.
Background and Aim
Helicobacter pylori
(
H. pylori
) infection causes extra-gastrointestinal as well as gastric diseases. This analytical cross-sectional study was performed to investigate the ...association between
H. pylori
infection and metabolic syndrome in a Korean population.
Methods
Anthropometric and metabolic data, as well as anti-
H. pylori
IgG antibodies, were measured in 21,106 subjects who participated in a health checkup between January 2016 and June 2017. The classification of metabolic syndrome followed the revised National Cholesterol Education Program criteria.
Results
After excluding subjects with a history of
H. pylori
eradication therapy, or gastric symptoms, the seropositivity of
H. pylori
was 43.2% in 15,195 subjects.
H. pylori
-positive participants had significantly higher body mass index (BMI), waist circumference, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and lower high-density lipoprotein (HDL-C) than did seronegative participants (
P
< 0.05). After adjusting for confounders, high TC, low HDL-C, and high LDL-C were associated with
H. pylori
seropositivity. Finally, the prevalence of metabolic syndrome was higher in
H. pylori
-seropositive subjects than in negative ones (27.2% vs. 21.0%,
P
< 0.05), and
H. pylori
seropositivity increased the likelihood of metabolic syndrome (OR 1.19, 95% CI 1.09–1.31,
P
< 0.001) after adjusting for sex, age, BMI, smoking, residence, household income, and education level. However, the association between
H. pylori
seropositivity and metabolic syndrome disappeared in those ≥ 65 years old.
Conclusions
H. pylori
infection plays an independent role in the pathogenesis of metabolic syndrome in Koreans under 65 years old.
Early and accurate detection of bacterial pathogens in the blood is the most crucial step for sepsis management. Gram‐negative bacteria are the most common organisms causing severe sepsis and ...responsible for high morbidity and mortality. We aimed to develop a method for rapid multiplex identification of clinically important Gram‐negative pathogens and also validated whether our system can identify Gram‐negative pathogens with the cell‐free plasm DNA from infected blood. We designed five MLPA probe sets targeting the genes specific to major Gram‐negative pathogens (uidA and lacY for E. coli, ompA for A. baumannii, phoE for K. pneumoniae, and ecfX for P. aeruginosa) and one set targeting the CTX‐M group 1 to identify the ESBL producing Gram‐negative pathogens. All six target‐specific peaks were clearly separated without any non‐specific peaks in a multiplex reaction condition. The minimum detection limit was 100 fg of pathogen DNA. When we tested 28 Gram‐negative clinical isolates, all of them were successfully identified without any non‐specific peaks. To evaluate the clinical applicability, we tested seven blood samples from febrile patients. Three blood culture positive cases showed E. coli specific peaks, while no peak was detected in the other four culture negative samples. This technology can be useful for detection of major sepsis‐causing, drug‐resistant Gram‐negative pathogens and also the major ESBL producing Gram‐negatives from the blood of sepsis patients in a clinical setting. This system can help early initiation of effective antimicrobial treatment against Gram‐negative pathogens for sepsis patients, which is very crucial for better treatment outcomes.
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