ABSTRACT
BackgroundLipid metabolism plays an important role in viral infections. Large cohort study suggested a protective potential of lipid-lowering drugs in COVID-19 outcomes, but the nature of observational study precludes it to draw a causal inference. ObjectivesTo assess the causal effect of lipid-lowering drugs (HMGCR inhibitors, PCSK9 inhibitors and NPC1L1 inhibitors) on COVID-19 outcomes using 2-sample Mendelian Randomization (MR) study. MethodsWe used two kinds of genetic instruments to proxy the exposure of lipid-lowering drugs, including expression quantitative trait loci (eQTLs) of drugs target genes, and genetic variants within or nearby drugs target genes associated with low-density lipoprotein (LDL) cholesterol from genome-wide association study (GWAS). GWASs of COVID-19 outcomes (susceptibility, hospitalization and very severe disease) were obtained from the COVID-19 Host Genetics Initiative. Summary-data-based MR (SMR) and inverse-variance weighted MR (IVW-MR) were used to calculate the effect estimates. ResultsSMR analysis found that a higher expression of HMGCR was associated with a higher risk of COVID-19 hospitalization (OR=1.38, 95%CI=1.06-1.81; P=0.019). Similarly, IVW-MR analysis observed a positive association between HMGCR-mediated LDL cholesterol and COVID-19 hospitalization (OR=1.32, 95%CI=1.00-1.74; P=0.049). No consistent evidence from both SMR and IVW-MR analyses was found for the association of HMGCR inhibitors with COVID-19 susceptibility or very severe disease, or for the association of PCSK9 inhibitors and NPC1L1 inhibitor with COVID-19 outcomes. ConclusionsIn this 2-sample MR study, we found potential causal evidence that HMGCR inhibitors could reduce the risk of COVID-19 hospitalization. Further research is needed to explore the therapeutic role of statins for COVID-19.
ABSTRACT
Objective To explore the effect of peripheral blood genomic DNA methylation on the relationship between methyl donor status and risk of breast cancer.Methods A case-control study was conducted.Each three hundred breast cancer cases and controls were consecutively recruited.Food frequency questionnaire was used to collect dietary information.Amounts on folate,methionine,choline and betaine intake were calculated.Blood samples were collected for DNA extraction.Peripheral blood genomic DNA methylation was measured by using the Methyl FlashTM Methylated DNA Quantification Kit.Pathway analysis was used to examine the effect of genomic DNA methylation on the relations between methyl donor status and risk of breast cancer.Results The genome DNA methylation rates were 0.46％ ± 0.25％ and 0.53％ ± 0.34％,respectively on both cases and controls,with differences statistically significant (P＜0.01).Results from the pathway analysis,results showed that methionine consumption was related to genomic DNA methylation (β=0.065,P＜ 0.05) while genomic DNA methylation was related to the risk of breast cancerk (β =-0.027,P＜ 0.05),respectively.Conclusions The level of peripheral blood genomic DNA methylation in breast cancer cases was significantly lower than that in the controls.Genomic DNA methylation seemed to have played a mediated role between methionine and the risk of breast cancer.
ABSTRACT
Objective To explore the effect of peripheral blood genomic DNA methylation on the relationship between methyl donor status and risk of breast cancer.Methods A case-control study was conducted.Each three hundred breast cancer cases and controls were consecutively recruited.Food frequency questionnaire was used to collect dietary information.Amounts on folate,methionine,choline and betaine intake were calculated.Blood samples were collected for DNA extraction.Peripheral blood genomic DNA methylation was measured by using the Methyl FlashTM Methylated DNA Quantification Kit.Pathway analysis was used to examine the effect of genomic DNA methylation on the relations between methyl donor status and risk of breast cancer.Results The genome DNA methylation rates were 0.46％ ± 0.25％ and 0.53％ ± 0.34％,respectively on both cases and controls,with differences statistically significant (P＜0.01).Results from the pathway analysis,results showed that methionine consumption was related to genomic DNA methylation (β=0.065,P＜ 0.05) while genomic DNA methylation was related to the risk of breast cancerk (β =-0.027,P＜ 0.05),respectively.Conclusions The level of peripheral blood genomic DNA methylation in breast cancer cases was significantly lower than that in the controls.Genomic DNA methylation seemed to have played a mediated role between methionine and the risk of breast cancer.
