Adil Abozaid Eissa

To assess the roles of genetic modifiers in Iraqi beta-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 beta-thalassemia were further investigated for alpha-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: beta(+) alleles, HBG2 rs7482144, alpha-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 beta-thalassemia phenotype among Iraqis may pave the way to personalized medicine in this patient's group.

BACKGROUND: The current study was initiated to evaluate the comparability of fetomaternal hemorrhage (FMH) measurement using flow cytometry (FCM) and Kleihauer–Betke test (KBT) and also to evaluate the validity of the current anti-D immunoglobulin doses for the prevention of hemolytic disease of the newborn in Duhok/Iraq. MATERIALS AND METHODS: The current study included 101 pregnant women with Rh(D)-negative blood group who had Rh (D)-positive husbands. Their blood was tested for blood groping, FMH by FCM and KBT, and indirect Coombs test, 1 h following sensitizing events and 72 h after giving anti-D. Furthermore, blood from newborns was examined for blood group and direct Coombs test. RESULTS: The main sensitizing event was parturition (62.4%) followed by cesarean section (32.7%). The indirect Coombs was positive in 32 cases while the direct Coombs test was positive in 19 cases. In 63.4% of cases, the ABO blood groups were incompatible between mothers and their babies. When FMH was checked by KBT method, it was found that 16 (15.8%) participants had FMH ranging 1.2–51 mL (median 4.35 mL), while FMH was positive in 27 (26.7%) participants by FCM method ranging 1.2–54.4 ml (median 9.5 mL). About 4–5 patients had FMH (measured by KBT and FCM, respectively) of >12 mL and only 1% had a volume of >30 mL. The difference between KBT and FCM for FMH measurement was statistically significant with P < 0.001 when assessed by paired t-test and has a highly significant positive correlation with each other. The correlation of FMH was statistically significant with maternal gravidity, number of anti-D received before (moderate positive correlation), gestational age, and newborn hemoglobin (negative correlation). However, the correlation was not significant between FMH and the following factors: maternal parity, maternal hematological parameters, and ABO compatibility of mother and their babies with P > 0.05. CONCLUSION: Inadequate doses of anti-D had been given previously that resulted in sensitization in at least one-quarter of the cases, and this necessitated proper measurement of FMH in all Rh (D) mothers following sensitizing events.

The gene for coagulation factor VIII in hemophilia has more than 250 distinct mutations, and documentation of these mutations can predict the clinical phenotype, the likelihood of developing an FVIII inhibitor, and how an individual will react to the induction of immune tolerance. The current study set out to identify common mutations underlying hemophilia in a single center from Duhok/Iraq. All enrolled patients had molecular studies using inverse shifting PCR (IS-PCR) and limited sequencing to

Alpha thalassemia and hemoglobin F concentration are major modulators of sickle cell disease in many populations. To address the impact of these two modulators on phenotype in sickle cell disease patients from Northern Iraq this study was initiated. Seventy-four Iraqi patients with sickle cell anemia or sickle/β0 thalassemia in steady state were enrolled. They had a median age of 16 years and included 56.8% males. Patients were clinically evaluated and had their blood and reticulocyte count

J Indian Prosthodont Soc, Official publication of Indian Prosthodontic Society

(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.

Immigration impact on genetic epidemiology of thalassemia worldwide is well-recognized. Over the past decade, the Duhok Province of Northern Iraq attracted a large number of immigrants. To assess whether immigration had contributed to changes in the mutation spectrum of β-thalassemia (β-thal) in the region, we recruited 218 registered patients with symptomatic β-thal. The recruited patients included 50 (22.9%) from resettled migrant families. A total of 431 β-thal alleles were fully characterized, with 20 different thalassemia mutations, the most frequent being IVS-II-1 (G>A) (HBB: c.315 + 1G>A), IVS-I-6 (T>C) (HBB: c.92 + 6T>C), codon 5 (–CT) (HBB: c.17_18delCT), IVS-I-110 (G>A) (HBB: c.93-21G>A), codon 44 (–C) (HBB: c.135delC), codon 8 (–AA) (HBB: c.25_26delAA) and IVS-I-1 (G>A) (HBB: c.92 + 1G>A) constituting 72.8% of the total. Some differences in mutation spectrum were observed compared to earlier studies from this same province, the most notable of which were the higher frequencies of IVS-I-110 and codon 8. Interestingly, the highest proportions of alleles related to immigrants were encountered in these two allele groups. Ethnic variation was also documented, so that while Muslim Kurds had IVS-II-1, IVS-I-6, IVS-I-110, codon 5 and codon 44 as their most frequent mutations, the most frequent among Kurdish Yazidis, were codon 5, codon 44, codon 8 and IVS-I-6. These ethnic variations and changes in mutation spectrums are important and should be taken in consideration to ensure effective implementation of the thalassemia preventive program.

Background. Immune thrombocytopenic purpura (ITP) is considered to be one of the common childhood autoimmune diseases, and the current study was initiated to study the effect of various factors, particularly interleukin 1 receptor antagonist (IL-1Ra) gene polymorphism, on the course of the disease. Methods. The current case-control study involved 60 newly diagnosed children presented with ITP (also included 60 age- and sex-matched healthy children). All enrolled individuals had complete blood count and molecular study to determine the polymorphic state of IL-1Ra gene using conventional polymerase chain reaction. Results. Sixty patients with ages 1-14 years and having a male/female ratio of 1 : 1.61 were enrolled in the current study. Forty-five children (75%) recovered within the first year, and 15 (25%) children developed chronic ITP. IL-1Ra ∗ 2 variant was found to be significantly associated with control groups ( P = 0.011 ), while IL-1Ra ∗ 3 was significantly associated with patients ( P = − 0.0163 ). Other factors having significant association with the remission rate include a previous history of immunization ( P < 0.0001 ) and the symptoms at presentation ( P = 0.0009 ). Conclusions. The current study revealed a significant correlation of IL-1Ra gene polymorphism to the etiology and the course of the disease.

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.

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.