Lack of association between the eNOS rs1800779 (A/G) polymorphism and the myocardial infarction incidence among the Iraqi Kurdish population.

Objectives: The genetic polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are strongly associated with several cardiovascular diseases (CVDs) in various populations. The current study aimed to investigate the association of the eNOS rs1800779 (A/G) polymorphism with the progress of myocardial infarction (MI). Methods: Eighty-five healthy subjects and 80 patients with MI admitted to the Erbil Cardiac Centre in the Kurdistan Region of Iraq were enrolled in the study. All participants were Kurdish from the same ethnic group. The amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used to determine the rs1800779 (A/G) polymorphism of eNOS, and the nitric oxide (NO) serum level was detected by spectrophotometer. Results: The genotypic frequencies of the eNOS rs1800779 AA (wild type), AG, and GG were 58.75%, 33.75%, and 7.50%, respectively, in the MI patients, and 49.41%, 43.53%, and 7.06%, respectively, for the control group. The frequencies of the A and the G alleles were 75.6% and 24.4%, respectively, in the MI group, and 71.2% and 28.8%, respectively, in the control subjects. The results revealed a lack of association of the rs1800779 genotype distribution with the level of NO serum and increased risk of MI. Conclusion: The study concluded that there is a lack of association between the genotypes and alleles of the rs1800779 eNOS and susceptibility to MI in the studied population.

The severity of COVID-19 in hypertensive patients is associated with mirSNPs in the 3' UTR of ACE2 that associate with miR-3658: In silico and in vitro studies.

The SARS-CoV-2 virus targets the antigen converting enzyme 2 (ACE2) receptor, thus resulting in elevated morbidity and an increased risk of severe and fatal COVID-19 infection in individuals with hypertension and diabetes mellitus. Objectives: This study aimed to identify the association between increased susceptibility and severity in order to evaluate their impact in hypertensive COVID-19 patients using in vitro and in silico models. Methods: We identified 80 miRNA binding sites on ACE2 (for different miRNAs) as well as various 30 SNPs in the miRNA binding sites of the 3' untranslated region (3' UTR) in the ACE2 gene using different online software and tools. From August 2020 to August 2021, a total of 200 nasopharyngeal/mouth swabs samples were collected from Multan, Pakistan. In order to quantify the cDNA of ACE2 and miR-3658 genes, we used Rotor Gene qRT-PCR on hypertensive patients with COVID-19 as well as healthy controls. Results: Interestingly, the binding site of miR-3658 corresponding to the 3' UTR of ACE2 featured three SNPs (rs1457913029, C>T; rs960535757, A>C, G; rs1423809569, C>T), and its genomic sequence featured a single SNP (rs1024225815, C>T) with the same nucleotide variation (rs1457913029, C>T) which potentially increases the severity of COVID-19. Similarly, three other SNPs (rs1557852115, C>G; rs770335293, A>G; rs1024225815, C>T) were also found on the first binding site positions of miR-3658. Our in vitro study found that ACE2 gene expression had an effect on miR-3658 in COVID-19 patients who also had hypertension. In both cases, our analysis demonstrated that the in silico model captured the same biological mechanisms as the in vitro system. Conclusion: The identified SNPs could represent potential informative signatures owing to their position in the splicing site of the ACE2 gene.

Cardiac, Hepatic and Renal Dysfunction and IL-18 Polymorphism in Breast, Colorectal, and Prostate Cancer Patients.

INTRODUCTION: The present study aimed to determine the alterations in the serum levels of tumor markers used to evaluate cardiac, renal and liver function, and detect the interleukin (IL)-18 rs1946518 polymorphism in breast (BC), colorectal (CRC) and prostate cancer (PCa) patients. METHODS: Blood samples were collected from 65 female BC, 116 CRC, 79 PCa and 88 myocardial infarction (MI) patients, and 110 healthy individuals to determine the concentration of tumor and cardiac markers. Furthermore, the IL-18 rs1946518 polymorphism was assessed using amplification refractory mutation system (ARMS)-PCR. RESULTS: The serum levels of the tumor markers cancer antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and total prostate-specific antigen (TPSA) were significantly increased in cancer patients compared with healthy controls. Furthermore, the activity of high-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase­myocardial band (CK-MB) was enhanced in MI patients, however, their activity was unchanged in cancer patients. The activity of alkaline phosphatase (ALP), and the serum concentration of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea were markedly elevated in CRC and PCa patients, respectively, compared with the control group. Although, no significant differences were observed in the -607 C/A polymorphism and allele frequency of IL-18 among BC, CRC patients and healthy individuals, the odds ratio (OR) was 1.75 for both C and A allele in BC patients. Therefore, the -607 C/A polymorphism could be considered as a risk factor for BC. CONCLUSION: The aforementioned results suggested that tumor markers could be considered as excellent biomarkers for the early detection of BC, CRC and PCa, whereas the concentration of liver enzymes could serve as an alternative indicator for the diagnosis of CRC and PCa. Additionally, the rs1946518 polymorphism in the IL-18 gene could be considered as a risk factor for the occurrence of BC, CRC and PCa.
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