The rapidly developing research field of epitranscriptomics has recently emerged into the spotlight of researchers due to its vast regulatory effects on gene expression and thereby cellular physiology and pathophysiology. N6-methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) are among the most prevalent and well-characterized modified nucleosides in eukaryotic RNA. Both of these modifications are dynamically regulated by a complex set of epitranscriptomic regulators called writers, readers, and erasers. Altered levels of m6A and also several regulatory proteins were already associated with diabetic tissues. This review summarizes the current knowledge and gaps about m6A and m6Am modifications and their respective regulators in the pathophysiology of diabetes mellitus. It focuses mainly on the more prevalent type 2 diabetes mellitus (T2DM) and its treatment by metformin, the first-line antidiabetic agent. A better understanding of epitranscriptomic modifications in this highly prevalent disease deserves further investigation and might reveal clinically relevant discoveries in the future.

• Keywords
• RNA, T2DM, diabetes, epigenetics, epitranscriptomics, m6A, m6Am, type 2 diabetes mellitus,
• MeSH
• Adenosine metabolism   MeSH
• Diabetes Mellitus, Type 2 * genetics   MeSH
• Humans MeSH
• RNA, Messenger metabolism   MeSH
• RNA Processing, Post-Transcriptional MeSH
• RNA genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Adenosine MeSH
• RNA, Messenger MeSH
• RNA MeSH

Genetic predispositions may influence geographical and interethnic differences in COVID-19 prevalence and mortality in affected populations. Of the many genes implicated in COVID-19 progression, a substantial number have no direct functional link on virus transfer/viability or on the host immune system. To address this knowledge deficit, a large number of in silico studies have recently been published. However, the results of these studies often contradict the findings of studies involving real patients. For example, the ACE2 has been shown to play an important role in regulating coronavirus entry into cells, but none of its variations have been directly associated with COVID-19 susceptibility or severity. Consistently was reported that increased risk of COVID-19 is associated with blood group A and with the APOE4 allele. Among other genes with potential impacts are the genes for CCR5, IL-10, CD14, TMPRSS2 and angiotensin-converting enzyme. Variants within the protein-coding genes OAS1 and LZTFL1 (transferred to the human genome from Neanderthals) are understood to be among the strongest predictors of disease severity. The intensive research efforts have helped to identify the genes and polymorphisms that contribute to SARS-CoV-2 infection and COVID-19 severity.

• MeSH
• ABO Blood-Group System genetics   MeSH
• Angiotensin-Converting Enzyme 2 genetics   MeSH
• Apolipoproteins E genetics   MeSH
• COVID-19 genetics   virology   MeSH
• Heredity MeSH
• Phenotype MeSH
• Genetic Predisposition to Disease MeSH
• Risk Assessment MeSH
• Host-Pathogen Interactions MeSH
• Humans MeSH
• Polymorphism, Genetic * MeSH
• Disease Progression MeSH
• Risk Factors MeSH
• SARS-CoV-2 pathogenicity   MeSH
• Serine Endopeptidases genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• ABO Blood-Group System MeSH
• ACE2 protein, human MeSH Browser
• Angiotensin-Converting Enzyme 2 MeSH
• ApoE protein, human MeSH Browser
• Apolipoproteins E MeSH
• Serine Endopeptidases MeSH
• TMPRSS2 protein, human MeSH Browser

Cardiovascular disease (CVD) is a major cause of death around the world, with highest prevalence reported in minority Roma/Gypsy populations living in developed countries. Whether these differences are caused by unhealthy lifestyles or genetic factors remain unknown. The aim of our study was to examine the genotype frequencies of the rs10757274 polymorphism in the 9p.21 locus within ANRIL (antisense non-coding RNA in the INK4 locus), a long non-coding RNA located in the vicinity of the CDKN2A/2B inhibitors loci. ANRIL is understood to be the strongest genetic determinant of CVD in Caucasians. Using PCR-RFLP, we analysed the ANRIL rs10757274 polymorphism in 298 non-Roma (50% male) and 302 Roma/Gypsy (50% male) adult (39.5 ± 15.1 years and 39.2 ± 12.8 years, respectively) subjects. We found that frequencies of the ANRIL GG, GA and AA genotypes were 20.1%, 52.4% and 27.5% in the majority population and 32.9%, 47.9% and 19.2% in Roma/Gypsy subjects, respectively. The distribution of genotypes was deemed significantly different at P < 0.001. Within the Roma/Gypsy population, we detected increased prevalence of the CVD-associated GG genotype. Increased prevalence of CVD among Roma/Gypsies subjects may be significantly linked to genetic background.

• Publication type
• Journal Article MeSH

Despite the rapid progress in diagnosis and treatment of cardiovascular disease (CVD), this disease remains a major cause of mortality and morbidity. Recent progress over the last two decades in the field of molecular genetics, especially with new tools such as genome-wide association studies, has helped to identify new genes and their variants, which can be used for calculations of risk, prediction of treatment efficacy, or detection of subjects prone to drug side effects. Although the use of genetic risk scores further improves CVD prediction, the significance is not unambiguous, and some subjects at risk remain undetected. Further research directions should focus on the "second level" of genetic information, namely, regulatory molecules (miRNAs) and epigenetic changes, predominantly DNA methylation and gene-environment interactions.

• Keywords
• cardiovascular disease, epigenetic, gene, gene score, interaction, polymorphism,
• MeSH
• Genome-Wide Association Study methods   MeSH
• Genetic Predisposition to Disease MeSH
• Genetic Testing methods   MeSH
• Precision Medicine methods   MeSH
• Cardiovascular Diseases diagnosis   genetics   therapy   MeSH
• Humans MeSH
• Nutrigenomics methods   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH