A Population-Oriented Genetic Scoring System to Predict Phenotype: A Pathway to Personalized Medicine in Iraqis With ß-Thalassemia.

To assess the roles of genetic modifiers in Iraqi ß-thalassemia patients, and determine whether a genotype-based scoring system could be used to predict phenotype, a total of 224 Iraqi patients with molecularly characterized homozygous or compound heterozygous ß-thalassemia were further investigated for α-thalassemia deletions as well as five polymorphisms namely: rs7482144 C > T at HBG2, rs1427407 G > T and rs10189857 A > G at BCL11A, and rs28384513 A > C and rs9399137 T > C at HMIP. The enrolled patients had a median age of 14 years, with 96 males and 128 females. They included 144 thalassemia major, and 80 thalassemia intermedia patients. Multivariate logistic regression analysis revealed that a model including sex and four of these genetic modifiers, namely: ß+ alleles, HBG2 rs7482144, α-thalassemia deletions, and BCL11A rs1427407 could significantly predict phenotype (major versus intermedia) with an overall accuracy of 83.9%. Furthermore, a log odds genetic score based on these significant predictors had a highly significant area under curve of 0.917 (95% CI 0.882-0.953). This study underscores the notion that genetic scoring systems should be tailored to populations in question, since genetic modifiers (and/or their relative weight) vary between populations. The population-oriented genetic scoring system created by the current study to predict ß-thalassemia phenotype among Iraqis may pave the way to personalized medicine in this patient's group.

G6PD Deficiency Prevalence as a Cause of Neonatal Jaundice in a Neonatal Ward in Dohuk, Iraq.

OBJECTIVE: The current study initiated to address the effect of glucose-6-phosphate dehydrogenase (G6PD) deficiency on the pathogenesis and the severity of neonatal hyperbilirubinemia (NHB). STUDY DESIGN: A total of 100 newborns with moderate to severe indirect hyperbilirubinemia and 50 normal neonates without hyperbilirubinemia had been enrolled in the current case-control study. All enrolled neonates had been tested for ABO and Rh(D) blood grouping, Total serum bilirubin measurement, complete blood count, morphology, reticulocyte counts, direct Coombs' test, and G6PD enzyme assay. RESULTS: From all enrolled hyperbilirubinemic neonates, 16% were G6PD deficient and this displays a statistically significant difference in comparison to controls (only 6% were G6PD deficient). Also, significant difference was found in the level of serum indirect bilirubin among G6PD-deficient neonate in comparison to G6PD nondeficient neonates which had contributed significantly to the difference in the duration of phototherapy and hospitalization among deficient neonate. Despite this, no significant difference found in the onset of presentation, reticulocytes count, and age of neonates between the two groups (G6PD-deficient and G6PD nondeficient neonates). CONCLUSION: The current study augments the etiological role of G6PD in the causation and severity of NHB in the region; however, in the absence of significant difference in the reticulocytes and the hemoglobin level, the underlying mechanism cannot be backed to the excess hemolysis alone.

COVID-19 Disease and Associated Thrombocytopenia: Pathogenesis and a Clue to the Etiology.

(1) Background: Hospital mortality in patients suffering from SARS-CoV-2 infection has been associated with thrombocytopenia. The present study was conducted to establish the correlation of thrombocytopenia and the severity of infection. The impact of IL-1Ra gene polymorphism on the incidence and severity of thrombocytopenia was also studied. (2) Methods: Various biochemical parameters measured in all the 1200 enrolled patients included full blood counts, renal and liver function tests, iron study, inflammatory markers, and coagulation assays. A further 70 patients each were selected from the severe thrombocytopenic and non-thrombocytopenic patient groups to study the IL-1Ra gene polymorphism by RCR. (3) Results: Out of 1200 patients, 436 (36.3%) had thrombocytopenia. Among these patients, 118 (27.1%), 75 (17.2%), and 42 (9.6%) had mild, moderate, severe, and very severe thrombocytopenia, respectively. Severe cases mostly resulted from peripheral consumption (73.5%), hemo-phagocytosis (15.4%), and bone marrow suppression (11.11%). A statistically significant correlation was found between the occurrence and severity of thrombocytopenia with perturbated levels of inflammatory markers and the presence of comorbidities. The IL-1Ra∗3 variant was found to be significantly associated with thrombocytopenia. The IL-1Ra∗2 variant was significantly seen among controls. (4) Conclusions: The present study revealed a significant correlation between thrombocytopenia and the severity of COVID-19 disease. Moreover, the IL-1Ra∗3 variant of IL-1Ra gene was associated with thrombocytopenia.

Impact Of TP53 Gene Promoter Methylation On Chronic Lymphocytic Leukemia Pathogenesis And Progression.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a malignant lymphoid disorder that results from the overgrowth of mature-looking lymphoid cells in the blood and lymphatic tissue. Various clinical presentations have been attributed to the disease as a result of the different underlying genetic and epigenetic alterations. The current study has been initiated to study the role of an epigenetic alteration affecting the promoter of the TP53gene on CLL pathogenesis and progression. METHODS: The current study involved 54 newly diagnosed patients presenting with CLL as well as 30 normal individuals as controls. After obtaining verbal consent, data collection was done and the blood collected from all enrolled individuals for hematological investigations as well as for molecular categorization of TP53 methylation status. Methylation-specific polymerase chain reaction (MS-PCR) technique was used to define the methylation status of the TP53 gene promoter that encompasses DNA extraction, bisulfite conversion, conventional PCR amplification, running on agarose gel and documentation. Finally, statistical analysis was done to assess any correlation of the TP53 epigenetic alteration to the disease etiology and the progression. RESULTS: In the current study, all controls and 42 of 54 patients show unmethylated TP53 gene promoter; on the other hand, the methylated promoter was detected among 12 patients with a p-value of 0.001. TP53 gene promoter methylation significantly linked to reduced platelet count (p-value of 0.047) and advanced stage at presentation (p-value of 0.076). No significant differences were seen among both methylated and unmethylated TP53 promoters in relation to the age of the affected individuals, total white blood cell counts and hemoglobin level of the affected individuals. CONCLUSION: The current study revealed a significant correlation of TP53 gene promoter methylation to chronic lymphocytic leukemia pathogenesis and lower platelet counts.