Relationship of vitamin D status and bone mass according to vitamin D-binding protein genotypes

BACKGROUND: Vitamin D-binding protein (DBP) may alter the biological activity of total 25-hydroxyvitamin D [25(OH)D]; this could influence on the effects of vitamin D in relation to bone mineral density (BMD) and fractures. Emerging data suggest that fetuin-A may be involved in bone metabolism. We aimed to investigate the influence of DBP gene polymorphism on the relationship of vitamin D status and fetuin-A levels to BMD and bone markers. METHODS: This cross-sectional study was part of a health survey of employees of the Electricity Generating Authority of Thailand (1,734 healthy subjects, 72% male). Fasting blood samples were assayed for 25(OH)D, fetuin-A, N-terminal propeptides of type 1 procollagen (P1NP), C-terminal cross-linking telopeptides of type I collagen (CTx-I), and DBP rs2282679 genotypes. L1–L4 lumbar spine and femoral BMD were measured using dual-energy X-ray absorptiometry. RESULTS: The DBP rs2282679 genotype distribution conformed to the Hardy–Weinberg equilibrium. There were no correlations between 25(OH)D levels and BMD and bone markers. But a trend of positive correlation was observed for the DBP genotypes with total hip BMD, and for the interaction between 25(OH)D and DBP genotypes with BMD at all femoral sites. We further analyzed data according to DBP genotypes. Only in subjects with the AA (common) genotype, 25(OH)D levels were positively related to BMD and bone markers, while fetuin-A was negatively related to total hip BMD, independently of age, gender and BMI. CONCLUSIONS: The interaction between vitamin D status, as measured by circulating 25(OH)D and DBP rs2282679 genotypes, modified the association between 25(OH)D and BMD and bone markers. Differences in DBP genotypes additionally influenced the correlation of fetuin-A levels with femoral BMD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12937-015-0016-1) contains supplementary material, which is available to authorized users

Environmental Lead Exposure, Catalase Gene, and Markers of Antioxidant and Oxidative Stress Relation to Hypertension: An Analysis Based on the EGAT Study

Lead has been linked to the development of hypertension via oxidative stress. Catalase plays an important role in the disposal of hydrogen peroxide in erythrocyte and its activity was determined by CAT gene. The aims of this study were to investigate (1) the association between blood levels of antioxidant markers such as catalase, superoxide dismutase, glutathione, glutathione peroxidase, oxidative stress-marker (malondialdehyde), and blood lead level and (2) the influence of genetic polymorphism of CAT gene (rs769217) on change in blood pressure in general population of EGAT study project. This is a cross-sectional study of 332 normotensive, 432 prehypertensive, and 222 hypertensive male subjects. Hypertensive subjects had significantly higher blood lead level (5.28 μg/dL) compared to normotensive (4.41 μg/dL) and prehypertensive (4.55 μg/dL) subjects (P&lt;0.05). These significant findings are also found in MDA levels. Moreover, individuals with TT genotype in hypertensive group had significantly higher blood lead and MDA levels (6.06 μg/dL and 9.67 μmol/L) than those with CC genotype (5.32 μg/dL and 8.31 μmol/L,P&lt;0.05). Our findings suggested that decreased blood catalase activity in this polymorphism together with low level lead exposure induced lipid peroxidation may be responsible for hypertension.</jats:p

Effects of imatinib and nilotinib on the whole transcriptome of cultured murine osteoblasts.

Numerous clinical observations have confirmed that breakpoint cluster region-abelson fusion oncoprotein tyrosine kinase inhibitors used in leukemia treatment alter bone physiology in a complex manner. The aim of the present study was to analyze the whole transcriptome of cultured murine osteoblasts and determine the changes following treatment with imatinib and nilotinib using Sequencing by Oligonucleotide Ligation and Detection next generation RNA sequencing. This study also aimed to identify candidate signaling pathways and network regulators by multivariate Ingenuity Pathway Analysis. Based on the right-tailed Fisher's exact test, significantly altered pathways including upstream regulators were defined for each drug. The correlation between these pathways and bone metabolism was also examined. The preliminary results suggest the two drugs have different mechanisms of action on osteoblasts, and imatinib was shown to have a greater effect on gene expression. Data also indicated the potential role of a number of genes and signaling cascades that may contribute to identifying novel targets for the treatment of metabolic bone diseases

The Association of Soluble IGF2R and IGF2R Gene Polymorphism with Type 2 Diabetes

The aim of this study is to investigate the insulin-like growth factor type 2 (IGF2R) gene and circulating soluble IGF2R in relation to type 2 diabetes (T2DM). Six hundred fifty-four subjects without history of diabetes were screened for diabetes by oral glucose tolerance test. In addition, 145 subjects with known diabetes were recruited from a local diabetes clinic. Circulating IGF2R levels were measured by ELISA method; plasma glucose was measured by colorimetric method; insulin levels were determined by chemiluminescent method; IGF2R gene rs416572 was genotyped using real-time PCR. The distributions of IGF2R genotypes were 69.2% CC, 27.8% CT, and 3.0% TT. The C allele was more commonly found in diabetes subjects, with a significant difference (P<0.01). In the presence of the T allele, circulating IGF2R levels were significantly lower (P<0.05). There was no significant difference in other potential confounders including age, sex, and BMI. Only circulating IGF2R, age, and BMI were independently associated with the degree of insulin resistance, as assessed by the HOMA model. It was found that age, sex, and BMI were associated with beta cell function. In conclusion, IGF2R gene polymorphism and circulating IGF2R are associated with T2DM

SARS-CoV-2 Surveillance in Hospital Wastewater: CLEIA vs. RT-qPCR

The utilization of wastewater as a community surveillance method grew during the COVID-19 epidemic. COVID-19 hospitalizations are closely connected with wastewater viral signals, and increases in wastewater viral signals can serve as an early warning indication for rising hospital admissions. While reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) is the most often used approach for detecting SARS-CoV-2 in wastewater, chemiluminescence enzyme immunoassay (CLEIA) is an alternative automated method. In two assays, 92 wastewater grab samples from a hospital were investigated for the presence of SARS-CoV-2, expected for continuous and monitoring SARS-CoV-2 surveillance. One was in the RT-qPCR nucleic acid test, and another was in the CLEIA assay quantitative antigen test. In 24/92 (26.09%) of the wastewater samples, RT-qPCR identified at least two SARS-CoV-2 genes (ORF1ab, N, or S genes). CLEIA, on the other hand, detected SARS-CoV-2 antigen in 39/92 (42.39%) of the samples. CLEIA demonstrated a low sensitivity and specificity of sensitivity of 54.2% (95% CI: 44.0&ndash;64.3%) and 61.8% (95% CI: 51.8&ndash;71.7%), respectively, as compared to RT-qPCR. The &kappa; coefficient indicated slight agreement between assay. Then, the CLEIA assay cannot replace molecular-based testing like RT PCR for determining SARS-CoV-2 in hospital wastewater

Gut Microbiota Characteristics in Children After the Use of Proton Pump Inhibitors

BACKGROUND/AIMS: Prolonged acid suppression from proton pump inhibitor (PPI) has been shown to cause gut microbiota alteration, which may increase the risk of various infections in adults. We aimed to characterize gut microbiota profiles in children after a short-term use of PPI. MATERIALS AND METHODS: Children aged 1-18 years who underwent PPI therapy were included during April-December 2017. We excluded children who previously used antibiotics or acid suppressants and who had a history of acute gastroenteritis or specific food avoidance one month prior to the enrolment. The stool samples before and after the PPI use were collected for gut microbiota composition. The 16S ribosomal RNA gene sequencing was performed by using Illumina MiSeq. The differences in the gut microbiota profile after the use of PPI were compared to pre-PPI period. RESULTS: We completed stool collection in 20 children (median age of 5.8 years and 60% were female). No significant changes in the overall number of species-level taxonomy categories or predominant bacteria belonging to the phylum (Bacteroidetes) were noted. We found a trend increase in the proportion of the phylum Firmicutes among children living in the designated metropolitan/suburban area (P = .07) and among males (P = .11). In four children with infection-related adverse effects, we noted a nonsignificant increase in the proportion of the phylum Firmicutes after the PPI use (from 35% to 52%, P = .14). CONCLUSIONS: Even the total number of and predominant gut microbiota did not significantly change after a four- to eight-week course of PPI therapy; we found a trend of increase in the proportion of the phylum Firmicutes in certain groups of children