Genotyping of the rare Para-Bombay blood group in southern Thailand

ABSTRACT Introduction: The para-Bombay phenotype, or H-deficient secretor, results from different mutations of the FUT1, with or without the FUT2 mutation. Consequently, there is an absent or weak expression of the H antigen on red blood cells (RBCs). Routine ABO blood grouping for two siblings with blood group O showed discrepant results with their parental blood group AB. Fragments encompassing the entire coding region of the FUT1 and FUT2 genes were investigated. Methods: Blood and saliva specimens were collected to verify the correct ABO grouping by cell grouping, serum grouping and the hemagglutination inhibition (HI) test, respectively. The FUT1 and FUT2 genomes were identified using the whole-exome sequencing (WES) in two children's DNA blood specimens and may have caused, or been relative to, their blood group. Genetic variations of the FUT1 and FUT2 genes have been investigated in the other family members using the Sanger sequencing. Results: The serologic reaction results of the proband revealed that A, B and H antigens were absent on RBCs, and that the serum contained anti-H. However, ABH and AH antigens were present in the saliva PB1 and PB2, respectively. The probands PB1 and PB2 were assigned as AB and A blood groups, respectively. Blood genotyping confirmed that heterozygous mutations of the FUT1 gene, c.551_552delAG, were identified. Three family members, PB3, PB, and PB8, also showed normal ABO blood groups, but their genotypes were also the FUT1 mutation c.551_552delAG. Conclusions: The FUT1 mutation c.551_552delAG may result in the reduced or absent H antigen production on RBCs, which characterizes the para-Bombay phenotypes. Blood genotyping is essential if these individuals need a blood transfusion or are planning to donate blood.

Upregulation of miR-20a-5p as the Potential MicroRNA Marker in Red Blood Cell Storage Lesion.

Background: Packed red blood cells (PRBCs) can be preserved for 42 days, and stored PRBCs have slow, dangerous changes over time during storage. miRNA is approximately 22 nucleotides long, a small single-stranded noncoding RNA molecule. miRNA guides by pairing bases with their downstream target mRNA to regulate negative expression. They are essential in many life processes, including cell differentiation, proliferation, and apoptosis. Therefore, miRNA alterations may represent possible biomarkers of PRBC storage lesions. This study is aimed at validating the miR-20a-5p in PRBC storage. Study Design and Methods. A total of 20 PRBC samples were divided into day 1 and day 20 storage groups. Total miRNA was extracted and quantified by probe-based RT-qPCR assays to explore the potential role of miRNAs in PRBC storage lesions. Results: Upregulated miR-20a-5p in PRBC storage on day 20 compared to day 1. MiR-20a-5p promoted cell survival, which may affect the downstream regulation and decrease PRBC viability in prolonged storage. Conclusion: On this basis, this detection may help to assess the quality of stored PRBCs.

A Systematic Review and Meta-Analysis of the Proportion Estimates of Disseminated Intravascular Coagulation (DIC) in Malaria.

Disseminated intravascular coagulation (DIC) is a potentially life-threatening condition that causes systemic coagulation to be turned on and coagulation factors to be used up. However, the evidence for DIC in malaria patients is still not clear, and small case series and retrospective studies have shown varying results. This meta-analysis was intended for the evaluation of the evidence of DIC among malaria patients using a meta-analysis approach. The protocol for the systematic review was registered at PROSPERO as CRD42023392194. Studies that investigated DIC in patients with malaria were searched in Ovid, Scopus, Embase, PubMed, and MEDLINE. The pooled proportion with 95% confidence intervals (CI) of DIC among malaria patients was estimated using a random-effects model. A total of 1837 articles were identified, and 38 articles were included in the meta-analysis. The overall proportion of DIC in malaria was 11.6% (95% CI: 8.9%-14.3%, I2: 93.2%, 38 studies). DIC in severe falciparum malaria and fatal malaria was 14.6% (95% CI: 5.0-24.3%, I2: 95.5%, 11 studies) and 82.2% (95% CI: 56.2-100%, I2: 87.3, 4 studies). The estimates of DIC among severe malaria patients who had multi-organ dysfunction with bleeding, cerebral malaria, acute renal failure, and ≥2 complications were 79.6% (95% CI: 67.1-88.2%, one study), 11.9% (95% CI: 7.9-17.6%, one study), 16.7% (95% CI: 10.2-23.3%, ten studies), and 4.8% (95% CI: 1.9-7.7%, nine studies), respectively. The proportion estimates of DIC among the patients with malaria depended on the Plasmodium species, clinical severity, and types of severe complications. The information from this study provided useful information to guide the management of malaria patients. Future studies are needed to investigate the association between Plasmodium infection and DIC and to understand the mechanism of malaria-induced DIC.

Association between Rhesus Blood Groups and Malaria Infection: A Systematic Review and Meta-Analysis.

In the literature, there was inconsistency in the risk of malaria between individuals with Rhesus blood group positive (Rh+) and negative (Rh-). The systematic review aimed to investigate the risk of malaria among participants with different Rh blood types. All observational studies that reported the occurrence of Plasmodium infection and investigation of the Rh blood group were searched in five databases (Scopus, EMBASE, MEDLINE, PubMed, and Ovid). Strengthening the Reporting of Observational Studies in Epidemiology was used to assess the reporting quality in the included studies. A random-effects model was used to calculate the pooled log OR and 95% confidence intervals (CIs). Database searches yielded a total of 879 articles, of which 36 were eligible for inclusion in the systematic review. The majority of the included studies (44.4%) revealed that Rh+ individuals had a lower proportion of malaria than Rh- individuals; however, the remaining studies revealed a higher or no difference in the proportion of malaria between Rh+ and Rh- individuals. Overall, with moderate heterogeneity, the pooled results showed no difference in malaria risk between patients with Rh+ and Rh- (p = 0.85, pooled log OR: 0.02, 95% CI: -0.20-0.25, I2: 65.1%, 32 studies). The current study found no link between the Rh blood group and malaria, even though there was a moderate amount of heterogeneity. Further studies using prospective designs and a definitive method for Plasmodium identification are needed to investigate the risk of Plasmodium infection in Rh+ individuals and increase the reliability and quality of these studies.

Genotyping of the rare Para-Bombay blood group in southern Thailand.

INTRODUCTION: The para-Bombay phenotype, or H-deficient secretor, results from different mutations of the FUT1, with or without the FUT2 mutation. Consequently, there is an absent or weak expression of the H antigen on red blood cells (RBCs). Routine ABO blood grouping for two siblings with blood group O showed discrepant results with their parental blood group AB. Fragments encompassing the entire coding region of the FUT1 and FUT2 genes were investigated. METHODS: Blood and saliva specimens were collected to verify the correct ABO grouping by cell grouping, serum grouping and the hemagglutination inhibition (HI) test, respectively. The FUT1 and FUT2 genomes were identified using the whole-exome sequencing (WES) in two children's DNA blood specimens and may have caused, or been relative to, their blood group. Genetic variations of the FUT1 and FUT2 genes have been investigated in the other family members using the Sanger sequencing. RESULTS: The serologic reaction results of the proband revealed that A, B and H antigens were absent on RBCs, and that the serum contained anti-H. However, ABH and AH antigens were present in the saliva PB1 and PB2, respectively. The probands PB1 and PB2 were assigned as AB and A blood groups, respectively. Blood genotyping confirmed that heterozygous mutations of the FUT1 gene, c.551_552delAG, were identified. Three family members, PB3, PB, and PB8, also showed normal ABO blood groups, but their genotypes were also the FUT1 mutation c.551_552delAG. CONCLUSIONS: The FUT1 mutation c.551_552delAG may result in the reduced or absent H antigen production on RBCs, which characterizes the para-Bombay phenotypes. Blood genotyping is essential if these individuals need a blood transfusion or are planning to donate blood.

High Expression of miR-483-5p Predicts Chemotherapy Resistance in Epithelial Ovarian Cancer.

BACKGROUND: Ovarian cancer is the most deadly cancer that requires novel diagnostics and therapeutics. MicroRNAs are viewed as essential gene regulatory elements involved in different pathobiological mechanisms of many cancers, including ovarian cancer. OBJECTIVE: This study examined the relationship between microRNA (miRNA) expression and response to platinum-based chemotherapy. METHODS: Genome-wide miRNA expression analysis was conducted using Epithelial Ovarian Cancer (EOC) tissues from 25 patients with 17 malignant tumors and eight benign ovarian tumors. Candidate miRNAs that respond to platinum-based chemotherapy were selected for validation by quantitative RT-PCR. RESULTS: Among 2,578 mature human miRNAs, high expression of miR-483-5p correlated with poor responses to platinum-based chemotherapy in EOC patients. Furthermore, high levels of miR-483-5p in the resistant group suppressed expression of the apoptotic regulator TAOK-1. CONCLUSION: A possible marker for the prediction of chemotherapy response and resistance in patients may be miR-483-5p. Choosing the right treatment for each patient with EOC can avoid the risk of developing chemotherapy resistance.

MicroRNA Expression Profiling of Epithelial Ovarian Cancer Identifies New Markers of Tumor Subtype.

BACKGROUND: Epithelial Ovarian Cancer (EOC) is often challenging to diagnose, even though histological examination. MicroRNA (miRNA or miRNA) is bound to the target messenger RNA (mRNA) due to which the mRNA molecules are silenced. The identification of miRNA expression- based EOC subtypes is considered a critical means of prognostication. So far, the studies on EOC subtypes have not been well characterized. OBJECTIVE: This study aimed to confirm the existence of miRNAs in EOC and to assess their potential as clinical biomarkers for EOC. METHODS: We sampled 25 ovarian tumor tissues from patients with human ovarian tumors (17 malignant; 12 serous EOC, five non-serous EOC, and eight benign ovarian tumors). miRNA microarray detection was performed to identify EOC miRNAs. Real-time PCR was adapted for the validation of differentially expressed miRNAs detected by microarray analysis related to hybridization intensity. RESULTS: The results confirmed that miRNAs exist in EOC, relative expression of EOC miRNAs demonstrated that the upregulation of miR-483-5p, and downregulation of miR-127-3p, and miR- 532-5p were significantly expressed in the malignant group than in the benign group at p < 0.05. Besides, miR-483-5p could also distinguish EOC subtypes between serous EOC and non-serous EOC, with a p < 0.05. CONCLUSION: A comprehensive miRNA expression profiling can help to refine subtype classification in EOC, opening new opportunities for identifying clinically applicable markers for improved stratification and diagnostics of ovarian tumors.

EGFL7 and RASSF1 promoter hypermethylation in epithelial ovarian cancer.

DNA methylation is one of the epigenetic mechanisms associated with gene expression and plays a key role as in activation and deactivation of oncogenes and tumor suppressor genes, respectively. This study employed DNA methylation array to identify methylated genes which are highly correlated with various phenotypes of epithelial ovarian cancer (EOC) in Thai patients and to quantify promoter CpG-island methylation of candidate genes. Tissues from patients with serous and non-serous EOC showed significantly higher promoter methylation of EGFL7 and RASSF1 compared to benign cases. These results indicate the potential of investigating promoter CpG-island methylation of cancer-associated genes as biomarkers of disease progression and even possibly of early detection.