The long non‐coding RNAs (lncRNAs) play a critical regulatory role in the host response to the viral infection. However, little is understood about the transcriptome architecture, especially lncRNAs pattern during the SARS‐CoV‐2 infection. In the present study, using publicly available RNA sequencing data of bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) samples from COVID‐19 patients and healthy individuals, three interesting findings highlighted: (a) More than half of the interactions between lncRNAs‐PCGs of BALF samples established by three trans‐acting lncRNAs (HOTAIRM1, PVT1 and AL392172.1), which also exhibited the high affinity for binding to the SARS‐CoV‐2 genome, suggesting the major regulatory role of these lncRNAs during the SARS‐CoV‐2 infection. (b) lncRNAs of MALAT1 and NEAT1 are possibly contributed to the inflammation development in the SARS‐CoV‐2 infected cells. (c) In contrast to the 3′ part of the SARS‐CoV‐2 genome, the 5′ part can interact with many human lncRNAs. Therefore, the mRNA‐based vaccines will not show any side effects because of the off‐label interactions with the human lncRNAs. Overall, the putative functionalities of lncRNAs can be promising to design the non‐coding RNA‐based drugs and to inspect the efficiency of vaccines to overcome the current pandemic.
The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. After analyzing TCGS data, 570 genetic variations on the ACE2 gene, including single nucleotide polymorphisms (SNP) and insertion/deletion (INDEL) were detected. Interestingly, two observed missense variants, K26R and S331F, which only the first one was previously reported, can reduce the receptor affinity for the viral Spike protein. Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered. As our results show that the genetic variation of ACE2 can at least influence the affinity of this receptor to its partners, we need to consider the genetic variations on ACE2 as well as other genes in the pathways that contribute to the pathogenesis of COVID-19 for designing efficient drugs and vaccines.
Biological processes involving environmental and genetic factors drive the interplay between age- and sex-regulating lipid profile. The relation between variations in the LPA gene with increasing the risk of coronary heart disease is dependent on population differences, sex, and age. The present study tried to do a gene candidate association analysis in people with myocardial infarction (MI) in a 22 year cohort family-based longitudinal cohort study, Tehran Cardiometabolic Genetic Study (TCGS). After adjusting p value by the FDR method, only the association of rs6415084 with the MI probability and the age-of-CHD-onset was significant in males in their middle age (p < 0.005). Surprisingly, a lack of association was observed for the rest of the markers (16 SNPs). These results revealed the moderator effects of age and sex on the association between the genetic variants (SNPs) of LPA and heart disease risk. Our observations may provide new insights into the biology that underlies lipid profile with age or the sexual dimorphism of Lp(a) metabolism. Finally, Lp(a) appears to be an independent risk factor; however, the role of sex and ethnicity is important.
The Tehran Cardiometabolic Genetic Study (TCGS) is a large population-based cohort study with periodic follow-ups, which created a comprehensive database of 20,367 participants born between 1911-2015 selected from 4 different longitudinal, ongoing, and family-based studies. The study aims to identify the potential targets for prevention and intervention for non-communicable diseases in mid-life and late life. The study focuses on cardiovascular, endocrine, metabolic abnormalities, cancers, and some inherited diseases. Since 2017, the cohort expanded the information by coding all health-related complications (hospitalization outcomes and self-reports) based on ICD11 coding and confirming the consanguineous marriage with genetic markers. This article presents an update on the rationale and design of the study. We also present a summary of our findings and our goals toward precision medicine.
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