MicroRNAs (miRNAs) are an abundant class of small nonprotein-coding RNAs with posttranscriptional regulatory functions as tumour suppressors and oncogenes. Aberrant expression and structural alteration of miRNAs are thought to participate in tumourigenesis and cancer development. It has been suggested that the presence of single-nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression, and/or binding to target mRNA and represent another type of genetic variability that can contribute to the development of human cancers. Recent studies have indicated that the miR-196a-2 rs11614913 (C→T) polymorphism could alter mature miR-196a-2 expression and target mRNA binding. To determine the association of the miR-196a-2 rs11614913 polymorphism with the risk of hepatocellular carcinoma (HCC) development in a Turkish population, a hospital-based case-control study was designed consisting of 185 subjects with HCC and 185 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the miR-196a-2 rs11614913 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Our data shows that the CC genotype of the miR-196a-2 rs11614913 polymorphism is associated with increased risk of HCC development in this Turkish population (OR = 2.41, 95% CI: 1.30-4.50, P = 0.005). Furthermore, according to stratified analysis, a significant association was observed between the homozygote CC genotype and HCC risk in the subgroups of male gender (OR = 3.12, 95% CI: 1.53-6.34, P = 0.002) and patients with hepatitis B virus (HBV)-related HCC (OR = 2.88, 95% CI: 1.33-6.22, P = 0.007). Because our results suggest for the first time that the miR-196a-2 rs11614913 polymorphism may be a genetic susceptibility factor for HCC (especially in the male gender and HBV-infected patients) in the Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different ethnic origins.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease 2019 (COVID-19), has been identified in China in late December 2019. SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA betacoronavirus of the Coronaviridae family. Coronaviruses have genetic proofreading mechanism that corrects copying mistakes and thus SARS-CoV-2 genetic diversity is extremely low. Despite lower mutation rate of the virus, researchers have detected a total of 12,706 mutations in the SARS-CoV-2 genome, the majority of which were single nucleotide polymorphisms. Sequencing data revealed that the SARS-CoV-2 accumulates two-single nucleotide mutations per month in its genome. Recently, an amino acid aspartate (D) to glycine (G) (D614G) mutation due to an adenine to guanine nucleotide change at position 23,403 at the 614th amino-acid position of the spike protein in the original reference genotype has been identified. The SARS-CoV-2 viruses that carry the spike protein D614G mutation have become dominant variant around the world. The D614G mutation has been found to be associated with 3 other mutations in the spike protein. Clinical and pseudovirus experimental studies have demonstrated that the spike protein D614G mutation alters the virus phenotype. However, the impact of the mutation on the rate of transmission between people, disease severity and the vaccine and therapeutic development remains unclear. Three variants of SARS-CoV-2 have recently been identified. They are B.1.1.7 (UK) variant, B.1.351 (N501Y.V2, South African) variant and B.1.1.28 (Brazilian) variant. Epidemiological data suggest that they have a higher transmissibility than the original variant. There are reports that some vaccines are less efficacious against the B.1.351 variant. This review article discusses the effects of novel mutations in the SARS-CoV-2 genome on transmission, clinical outcomes and vaccine development.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuing to evolve, emerging novel variants with spike protein mutations. Although most mutations emerged in the SARS-CoV-2 genome are neutral or mildly deleterious, a small number of mutations can affect virus phenotype that confers the virus a fitness advantage. These mutations can enhance viral replication, raise the risk of reinfection and blunt the potency of neutralizing antibodies triggered by previous infection and vaccination. Since December 2020, the SARS-CoV-2 has emerged five quickly spreading strains, designated variants of concern (VOCs), including the Alpha (B.1.1.7) variant, the Beta (B.1.351) variant, the Gamma (P.1) variant, the Delta (B.1.617.2) variant and the Omicron (B.1.1.529) variant. These variants have a high number of the mutations in the spike protein that promotes viral cell entry through the angiotensin-converting enzyme -2 (ACE2). Mutations that have arisen in the receptor binding domain (RBD) of the spike protein are of great concern due to their potential to evade neutralizing antibodies triggered by previous infection and vaccines. The Alpha variant emerged in the United Kingdom in the second half of 2020 that has spread quickly globally and acquired the E484K mutation in the United Kingdom and the United States. The Beta and Gamma variants emerged in South Africa and Brazil, respectively, that have additional mutations at positions E484 and K417 in the RBD. SARS-CoV-2 variants containing the combination of N501Y, E484K, and K417N/T mutations exhibit remarkably decreased sensitivity to neutralizing antibodies mediated by vaccination or previous infection. The Gamma variant may result in more severe disease than other variants do even in convalescent individuals. The Delta variant emerged in India in December 2020 and has spread to many countries including the United States and the United Kingdom. The Delta variant has 8 mutations in the spike protein, some of which can influence immune responses to the key antigenic regions of RBD. In early November 2021, the Omicron (B.1.1.529) variant was first detected in Botswana and South Africa. The Omicron variant harbors more than 30 mutations in the spike protein, many of which are located within the RBD, which have been associated with increased transmissibility and immune evasion after previous infection and vaccination. Additionally, the Omicron variant contains 3 deletions and one insertion in the spike protein. Recently, the Omicron variant has been classified into three sublineages, including BA.1, BA.2, and BA.3, with strikingly different genetic characteristics. The Omicron BA.2 sublineage has different virological landscapes, such as transmissibility, pathogenicity and resistance to the vaccine-induced immunity compared to BA.1 and BA.3 sublineages. Mutations emerged in the RBD of the spike protein of VOCs increase viral replication, making the virus more infectious and more transmissible and enable the virus to evade vaccine-elicited neutralizing antibodies. Unfortunately, the emergence of novel SARS-CoV-2 VOCs has tempered early optimism regarding the efficacy of COVID-19 vaccines. This review addresses the biological and clinical significance of SARS-CoV-2 VOCs and their impact on neutralizing antibodies mediated by existing COVID-19 vaccines.

Vitiligo is an autoimmune disease characterized by depigmentation of the skin due to destruction of melanocytes. Interferons have been used for the treatment of chronic hepatitis C and some malignancies. We report interferon alpha-2a-induced vitiligo in a male patient with chronic active hepatitis C. All skin lesions disappeared completely without requiring therapy after discontinuation of interferon. This case suggests that vitiligo may be developed during interferon therapy as a side effect.