overview: The more severe consequences of COVID-19 associated with age-related macular degeneration may result from genetic predisposition in addition to high levels of Pdgf in serum.
sauce: Boston University
Recent evidence suggests that age-related macular degeneration (AMD) is a clinical risk factor that increases the risk of infection and death. AMD has been reported to be at increased risk of severe complications of SARS-CoV-2 infection, including respiratory failure and death (25%), type 2 diabetes (21%) and obesity (13%). higher risk than
Given these observations, researchers at the Boston University Chobanian & Avedisian School of Medicine hypothesized that AMD and COVID-19 share common genetic risk factors, suggesting that the two diseases and genetic mutations We designed and performed a study to identify novel associations with PDGFB gene. This gene encodes platelet-derived growth factor (Pdgf), which is involved in the formation of new blood vessels and is involved in the abnormal vascular changes that occur in AMD.
They also found that more severe COVID-19 outcomes were associated with AMD, which likely resulted from a genetic predisposition to dysfunction involving complement proteins, and higher serum Pdgf levels. I also found
“Our findings add to the body of evidence for increased risk of infection and mortality from COVID-19 in AMD patients. It lends credence to previously reported clinical studies that found high risk and that this increased risk may have a genetic basis,” explained co-corresponding author Lindsay A. Farrer, Ph.D. I did, Chief of Biomedical Genetics.
The BU research team used large genetic datasets containing tens of thousands of people to identify genome-wide variants associated with each of the three outcomes of AMD and COVID-19: infection rate, critical illness, and hospitalization. conducted a search for These datasets were previously collected and studied separately for each genetic factor contributing to AMD risk and his COVID-19 disease outcome.
The researchers then analyzed published data from AMD or COVID-19 patients and controls to assess the association of the variants. PDGFB in genetic activity.
Finally, they employed analytical techniques that could explore causal relationships between them. PDGFB Outcomes for genetic variants, blood Pdgfb levels, AMD, and COVID-19.
According to researchers, these findings PDGFB Gene activity and serum PDGF concentrations may reduce the severity of COVID-19, especially among the elderly.
“Anti-VEGF therapy (the current treatment for AMD that limits the growth of blood vessels in the eye that can impair vision) combined with an antagonist (drug that binds to its receptor) to block PDGF signaling. The strategy is believed to be even more effective than single VEGF and is currently being investigated in clinical trials.”.
The researchers suggest that this finding of common genetic risk factors requires a larger sample size of critical illnesses and hospitalizations to identify common pathologies and risk factors that contribute to worse clinical outcomes for both disease states. I think we need to understand it better.
Funding: This work was supported by National Institutes of Health grants RF1 AG057519, R01 AG069453, R01 AG048927, U19 AG068753, and U01 AG062602.
About this AMD and COVID-19 research news
author: Gina DiGrabio
sauce: Boston University
contact: Gina DiGrabio – Boston University
image: image is public domain
See also
Original research: open access.
“Genome-wide multifaceted study identifies association between PDGFB and outcome of age-related macular degeneration and COVID-19 infectionBy Lindsey A. Farrar et al. Journal of Clinical Medicine
overview
Genome-wide multifaceted study identifies association between PDGFB and outcome of age-related macular degeneration and COVID-19 infection
Age-related macular degeneration (AMD) has been implicated as a risk factor for severe outcomes from COVID-19.
The shared genetic architecture between AMD and COVID-19 (critical illness, hospitalization, and infection) was determined using AMD genetic correlation and pleiotropic analyzes (i.e., cross-phenotype meta-analysis). (n = 33,976) and COVID-19 (n ≥ 1,388,342) and subsequent analysis including expression quantitative trait loci (eQTL), differential gene expression, and Mendelian randomization (MR). A significant genetic correlation was observed between AMD and COVID-19 infection (rG. = 0.10, p = 0.02) and new genome-wide significant associations identified are nearby PDGFB (best SNP: rs130651; p = 2.4 × 10−8) A multifaceted analysis of two diseases.
Disease risk alleles of rs130651 were significantly associated with increased gene expression levels. PDGFB in multiple organizations (best eQTL p = 1.8 × 10−11 in whole blood) and immune cells (best eQTL p = 7.1 × 10−20 in T cells). PDGFB expression was observed to be higher in AMD cases than in AMD controls {fold change (FC) = 1.02; p = 0.067}, and peak stage of COVID-19 symptoms (11-20 days after onset) compared to early/advanced stage (0-10 days) in COVID-19 patients aged 40 years or older (FC = 2.17; p = 0.03) and 50 years old (FC = 2.15; p = 0.04). In our MR analysis, responsibility for AMD risk due to complement system dysfunction {OR (95% CI); hospitalization = 1.02 (1.01–1.03), infection = 1.02 (1.01–1.03), serum cytokine PDGF-BB Elevated values {β (95% CI); critical illness = 0.07 (0.02–0.11)} are significantly associated with COVID-19 outcome.
Our study demonstrated that AMD liability is associated with increased risk of COVID-19 and that PDGFB may be responsible for severe COVID-19 outcomes in AMD patients.
