1.
Alcohol Consumption Is Associated with Poor Prognosis in Obese Patients with COVID-19: A Mendelian Randomization Study Using UK Biobank.
Fan, X, Liu, Z, Poulsen, KL, Wu, X, Miyata, T, Dasarathy, S, Rotroff, DM, Nagy, LE
Nutrients. 2021;(5)
Abstract
BACKGROUND Acute and chronic alcohol abuse has adverse impacts on both the innate and adaptive immune response, which may result in reduced resistance to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and promote the progression of coronavirus disease 2019 (COVID-19). However, there are no large population-based data evaluating potential causal associations between alcohol consumption and COVID-19. METHODS We conducted a Mendelian randomization study using data from UK Biobank to explore the association between alcohol consumption and risk of SARS-CoV-2 infection and serious clinical outcomes in patients with COVID-19. A total of 12,937 participants aged 50-83 who tested for SARS-CoV-2 between 16 March to 27 July 2020 (12.1% tested positive) were included in the analysis. The exposure factor was alcohol consumption. Main outcomes were SARS-CoV-2 positivity and death in COVID-19 patients. We generated allele scores using three genetic variants (rs1229984 (Alcohol Dehydrogenase 1B, ADH1B), rs1260326 (Glucokinase Regulator, GCKR), and rs13107325 (Solute Carrier Family 39 Member 8, SLC39A8)) and applied the allele scores as the instrumental variables to assess the effect of alcohol consumption on outcomes. Analyses were conducted separately for white participants with and without obesity. RESULTS Of the 12,937 participants, 4496 were never or infrequent drinkers and 8441 were frequent drinkers. Both logistic regression and Mendelian randomization analyses found no evidence that alcohol consumption was associated with risk of SARS-CoV-2 infection in participants either with or without obesity (All q > 0.10). However, frequent drinking, especially heavy drinking (HR = 2.07, 95%CI 1.24-3.47; q = 0.054), was associated with higher risk of death in patients with obesity and COVID-19, but not in patients without obesity. Notably, the risk of death in frequent drinkers with obesity increased slightly with the average amount of alcohol consumed weekly (All q < 0.10). CONCLUSIONS Our findings suggest that alcohol consumption has adverse effects on the progression of COVID-19 in white participants with obesity, but was not associated with susceptibility to SARS-CoV-2 infection.
2.
Decreased expression of CTR2 predicts poor prognosis of patients with clear cell renal cell carcinoma.
Xia, Y, Liu, L, Long, Q, Bai, Q, Wang, J, Xu, J, Guo, J
Urologic oncology. 2016;(1):5.e1-9
Abstract
PURPOSE Clear cell renal cell carcinoma (ccRCC) is well known for its hypervascularity due to the Von Hippel-Lindau/hypoxia-inducible factor dysregulation. Recent findings suggested that copper transporter 2 (CTR2) is also associated with angiogenesis through copper׳s modulation of the hypoxia-inducible factor pathway. Our group thus explored the prognostic role of CTR2 in patients with ccRCC. MATERIALS AND METHODS A total of 331 patients with ccRCC who underwent nephrectomy were enrolled between February 2005 and June 2007 at a single institution. The median follow-up was 98.97 months (2.63-120.47mo). Patients׳ samples were collected and stained for CTR2 by immunohistochemistry. The staining intensity was analyzed quantitatively and defined as high/low expression using X-tile software. Stage, Size, Grade, and Necrosis score and University of California Los Angeles Integrated Staging System score were applied to stratify patients׳ risks. Survival analyses were performed through the Kaplan-Meier method and Cox proportional hazard model. After integrating tumoral CTR2 expression with other clinical parameters, 2 nomograms were generated for overall survival (OS) and disease-free survival (DFS) prediction. RESULTS CTR2 expression in ccRCC was decreased compared with that in the peritumoral tissue (P<0.001) and negatively correlated with many other clinical parameters. In survival analyses using the Kaplan-Meier method, low tumoral CTR2 expression displayed a dismal prognostic effect both in OS and DFS prediction (P<0.001). Multivariate analyses also revealed the same result after adjusted with other clinical parameters (P<0.001). Stratifying patients into 3 risk levels using the Stage, Size, Grade, and Necrosis score and University of California Los Angeles Integrated Staging System score, decreased CTR2 expression associated with shorter OS and DFS in the low- and intermediate-risk groups. Moreover, the generated nomogram integrating tumoral CTR2 expression performed better in predicting patients׳ OS than using TNM stages alone (c-index = 0.799; 95% CI: 0.752-0.846 vs. 0.691; 95% CI: 0.637-0.745). CONCLUSIONS CTR2 is a novel prognostic marker for patients with ccRCC both in OS and DFS prediction, and could be incorporated with other clinical parameters for better patient risk stratification.
3.
Duodenal ferroportin is up-regulated in patients with chronic hepatitis C.
Ma, L, Zou, T, Yuan, Y, Lv, J, Dong, X, Yang, G, Zhu, Y, Luo, J, Zhang, Z, Yang, J
PloS one. 2014;(10):e110658
Abstract
Hepatitis C virus (HCV) infection is a leading cause of liver-related mortality. Chronic hepatitis C (CHC) is frequently associated with disturbances in iron homeostasis, with serum iron and hepatic iron stores being elevated. Accumulating evidence indicates that chronic HCV infection suppresses expression of hepatic hepcidin, a key mediator of iron homeostasis, leading to iron overload conditions. Since hepcidin mediates degradation of ferroportin, a basolateral transporter involved in the release of iron from cells, diminished hepcidin expression probably leads to up-regulation of ferroportin-1 (Fpn1) in patients with CHC. In this study, we determined the protein levels of duodenal Fpn1, and found that its expression was significantly up-regulated in patients with CHC. The expression of duodenal Fpn1 is negatively correlated with mRNA levels of hepcidin, and positively correlated with serum iron parameters. Although iron is a critical factor for growth of a variety of pathogenic bacteria, our results suggest that iron overload in blood does not increase the infection rate of bacteria in patients with CHC.