Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study

Background@#Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS). @*Methods@#We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed. @*Results@#rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles. @*Conclusion@#The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

A Case of Peritoneal Dialysis-related Peritonitis Caused by Aeromonas Hydrophila in the Patient Receiving Automated Peritoneal Dialysis

Peritoneal dialysis (PD)-related peritonitis is a major cause of injury and technique failure in patients undergoing PD. Aeromonas hydrophila is ubiquitous in the environment, and is a Gram-negative rod associated with infections in fish and amphibians in most cases; however, it can also cause opportunistic infections in immunocompromised patients. We report a case of A. hydrophila peritonitis in a 56-year-old male on automated PD. Peritonitis may have been caused by contamination of the Set Plus, a component of the automated peritoneal dialysis device. Although Set Plus is disposable, the patient reused the product by cleansing with tap water. He was successfully treated with intraperitoneally-administered ceftazidime and has been well without recurrence for more than 2 years.

Trends in Microorganisms Isolated from Blood Cultures at a Veterans Hospital from 2012 to 2015

Blood culture is important to detecting bacteremia and fungemia in patients with suspected sepsis. We observed a four-year trend of blood culture isolates in the frequency by age group and in vitro antimicrobial susceptibility patterns obtained at VHS Medical Center, the largest veterans hospital in Korea. Blood cultures collected between 2012 and 2015 were analysed retrospectively. Of 68,352 blood specimens, 7,901 isolates were identified during the study period. Seventy-two percent of the isolates were gram-positive cocci, 18% were gram-negative rods, and 6% were fungi. The frequency of bacteremia/fungemia in patients who were 80–89 years old was 43.8%, the highest rate among all age groups, and the mean age of patients diagnosed by blood culture was 77 years old. Coagulase-negative staphylococcus (52.3%), Staphylococcus aureus (8.3%), enterococci (7.5%), Escherichia coli (6.4%), and Klebsiella pneumoniae (3.9%) were the bacteria most commonly isolated. The percentage of methicillin-resistant S . aureus increased in 2015 (76%) relative to that in 2012–2014 (63%–65%), and that of vancomycin-resistant Enterococcus faecium was 17%–22% with no significant changes through time. Among the gram-negative isolates, the ciprofloxacin resistance rate increased to 51.4% (E. coli ) and 31.1% (K. pneumoniae ) in 2015, but imipenem or ertapenem resistance was still very rare, with resistance rates of less than 0.5%. Acinetobacter baumannii showed a high rate of resistance (over 70%) to imipenem and ciprofloxacin throughout the study. In Pseudomonas aeruginosa , the resistance rates of imipenem and ciprofloxacin increased dramatically over time. This analysis confirmed a decrease in antimicrobial susceptibility of gram-negative rods isolated by blood culture.

A Case of Rheumatoid Arthritis in a Patient with Bruton-Type Agammaglobulinemia

Bruton-type agammaglobulinemia is primary hypogammaglobulinemia followed by severe recurrent infection, including bacterial otitis media, bronchitis, pneumonia, and meningitis. Septic arthritis is a main musculoskeletal disorder that can occur in association with Bruton-type agammaglobulinemia. But the development of rheumatoid arthritis (RA) is rarely reported in a patient with hypogammaglobulinemia. Here, we describe a case of 34-year-old male with Bruton-type agammaglobulinemia, who presented with multiple symmetric polyarthritis. He was diagnosed as having a RA according to ACR criteria. His symptoms of polyarthritis had been improved after the introduction of medications including DMARDs (disease modifying anti-rheumatic drugs). Our case suggests that RA can be developed in the setting of agammaglobulinemia, and even in this situation, anti-rheumatic agents were effective to control arthritis without complication such as severe infection.

A Case of Histiocytic Sarcoma Presenting with Primary Bone Marrow Involvement

Histiocytic sarcoma (HS) is a very rare neoplasm that often shows an aggressive clinical course and systemic symptoms, such as fever, weight loss, adenopathy, hepatosplenomegaly and pancytopenia. It may present as localized or disseminated disease. We describe here a 63-yr-old male who manifested systemic symptoms, including fever, weight loss and generalized weakness. Abdominal and chest computed tomography failed to show specific findings, but there was suspicion of multiple bony changes at the lumbar spine. Fusion whole body positron emission tomography, bone scan and lumbar spine magnetic resonance imaging showed multiple bone lesions, suggesting a malignancy involving the bone marrow (BM). Several BM and bone biopsies were inconclusive for diagnosis. Necropsy showed replacement of the BM by a diffuse proliferation of neoplastic cells with markedly increased cellularity (95%). The neoplastic cells were positive for lysozyme and CD68, but negative for T- and B-cell lineage markers, and megakaryocytic, epithelial, muscular and melanocytic markers. Morphologic findings also distinguished it from other dendritic cell neoplasms.

Evaluation of Combination of BACTEC Mycobacteria Growth Indicator Tube 960 System and Ogawa Media for Mycobacterial Culture / 대한진단검사의학회지

BACKGROUND: The combined use of liquid media and solid media is recommended for mycobacterial culture. We evaluated diagnostic performance of combination of BACTEC Mycobacteria Growth Indicator Tube (MGIT; Becton Dickinson, USA) and 2% Ogawa media (Korean Institute of Tuberculosis, Korea) for recovery of mycobacteria. METHODS: In September 2007, 1,764 specimens from 1,059 patients were cultured with MGIT and Ogawa. Acid fast bacilli (AFB) smear was fluorochrome-stained. The isolates were identified into Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM) with PCR using Seeplex TB Detection Kit (Seegene, Korea). Recovery rate, time to detection (TTD), contamination rate, mixed growth rate and species distribution were analyzed. RESULTS: Two hundred thirty-five specimens (13.3%) from 165 patients (15.6%) were positive for mycobacterial culture. Recovery rates of mycobacteria from the group using both media, MGIT only, and Ogawa only were 13.3%, 12.1%, and 7.8%, respectively. While MGIT recovered 98.9% of MTB and 79.7% of NTM, Ogawa recovered 65.9% of MTB and 54.1% of NTM. TTDs of total mycobacteria/MTB/NTM in MGIT and Ogawa were 10.6/11.4/9.7 days and 31/29/33 days, respectively. MGIT TTDs of total mycobacteria/MTB/NTM from AFB-positive specimens were significantly shorter than those of AFB-negative specimens; 8.2/9.5/4.4 days vs 11.6/12.7/10.7 days. Contamination and mixed growth rate of MGIT were 9.6% and 3.7%. Primary culture of Ogawa recovered 1 MTB and 1 NTM among the 170 MGIT-contaminated specimens and 38 mycobacteria among 66 specimens that showed mixed cultures of MGIT. CONCLUSIONS: MGIT warrants sensitive and rapid isolation of mycobacteria. However, the combination of MGIT and Ogawa is more desirable to recover mycobacteria in the case of contaminations or mixed cultures.