The association of HBG2, BCL11A, and HMIP polymorphisms with fetal hemoglobin and clinical phenotype in Iraqi Kurds with sickle cell disease

Al-Allawi, Nasir; Qadir, Shatha M.; Puehringer, Helene; Chui, David H.K.; Farrell, John; Oberkanins, Christian

doi:10.1111/ijlh.12927

Cited by 9 publications

(7 citation statements)

References 40 publications

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“…This is in contrast to several earlier series of patients with SCD not treated with hydroxyurea that carry rs7482144 in the γ-globin promoter. These patients were characterized by increased HbF levels 9,22,32,33 and, in contrast to our findings, also less frequent vasoocclusive events 1, [34][35][36][37] . Studies on the association of rs7482144 with complications of SCD in patients treated with hydroxyurea are scarce 38 .…”

Section: Discussioncontrasting

confidence: 99%

Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea

et al. 2021

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The course of sickle cell disease (SCD) is modified by polymorphisms boosting fetal hemoglobin (HbF) synthesis. However, it has remained an open question how these polymorphisms affect patients who are treated with the HbF-inducing drug hydroxyurea/hydroxycarbamide. The German SCD registry offers the opportunity to answer this question, because >90% of patients are treated according to national guidelines recommending the use of hydroxyurea in all patients above 2 years of age. We analyzed the modifying effect of HbF-related genetic polymorphisms in 417 patients with homozygous SCD >2 years who received hydroxyurea. HbF levels were correlated with higher total hemoglobin levels, lower rates of hemolysis, a lower frequency of painful crises and of red blood cell transfusions. The minor alleles of the polymorphisms in the γ-globin promoter (rs7482144), BCL11A (rs1427407) and HMIP (rs66650371) were strongly associated with increased HbF levels. However, these associations did not translate into lower frequencies of vasoocclusive events that did not differ between patients either carrying or not carrying the HMIP and BCL11A polymorphisms. Patients on hydroxyurea carrying the γ- globin promoter polymorphism demonstrated substantially higher hemoglobin levels (p

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Section: Discussioncontrasting

confidence: 99%

Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea

et al. 2021

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“…El‐Hazmi et al described the genotypes and phenotypes of SCD in the Arab population in 2011 8 . Since then, there have been many new studies describing variants of SCD genotypes and phenotypes, and with the emerging era of gene therapy for SCD, it is essential to compile the current evidence, especially in the last 5 years 22‐44 . We will pool all data describing the genotypic and phenotypic variants of SCD in the Arab population to date in a systematic review.…”

Section: Discussionmentioning

confidence: 99%

Protocol for “Genetic composition of sickle cell disease in the Arab population: A systematic review”

Ata

Yousaf

Sardar

et al. 2022

Health Science Reports

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Background: Sickle Cell Disease (SCD) is a global health issue in hematology with a progressively increasing prevalence. There are recent advances in the management of SCD, with new drugs being introduced. It is essential to analyze the genetic makeup of SCD regionally to anticipate the effectiveness of management modalities. This systematic review's main objectives are (a) to combine the existing knowledge of the genetic composition of SCD in the Arab population and (b) to analyze the various phenotypes of SCD prevalent in the Arab population. Methods: We will perform a systematic review and search multiple electronic databases predefined search terms to identify eligible articles. Eligible studies should report findings on the genetic testing of Sickle Cell disease in the 22 Arab countries.Case reports, case series, observational studies with cross-sectional or prospective research design, case-control studies, and experimental studies will be included. Study quality will be independently evaluated by two reviewers using the statistical methodology and categories guided by the Cochrane Collaboration Handbook and PRISMA guidelines.Discussion: This review will explore and integrate the evidence available on the various genotypes and phenotypes of SCD in the Arab population. By acquiring and summarizing data about the genetic and phenotypic variants of the SCD patient population, this study will add to the knowledge and help find more precise treatments.

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“…Furthermore, the cumulative numbers of minor alleles of these polymorphisms were positively linked to hemoglobin concentration but negatively so to LDH, reticulocyte counts, leukocyte counts, transfusion, and pain frequencies. The study concluded that the cumulative number of minor alleles at the three aforementioned polymorphisms may serve as a better predictor of phenotypic variability of SCD, than each one on its own (Al-Allawi et al 2019).…”

Section: Molecular and Clinical Aspects Of Sickle Cell Disease Among Iraqi Kurdsmentioning

confidence: 97%

“…One of the major modifiers of disease severity in SCD is hemoglobin F; the latter is modulated mainly by three major quantitative trait loci (QTL) on chromosomes 11, 2, and 6 (Thein et al 2009). A recent study enrolled 128 Kurdish SCD patients to address the role of these QTLs in the phenotypic variability of this disorder (Al-Allawi et al 2019). The study documented that HBG2 rs7482144, BCL11A rs1427407, and HMIP rs9399137 contributed significant 18.1%, 14.3%, and 8.8% to HbF variability in Kurdish Iraqi SCD.…”

Section: Molecular and Clinical Aspects Of Sickle Cell Disease Among Iraqi Kurdsmentioning

confidence: 99%

Genetic epidemiology of hemoglobinopathies among Iraqi Kurds

2020

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Hemoglobinopathies are major health problems among Iraqi Kurds, who are a distinct ethnic group inhabiting North and Northeastern Iraq. We reviewed published literature on these disorders in this part of the world, and it was revealed that the most prevalent is β-thalassemia with carrier rates of 3.7-6.9%. Alpha thalassemia is less prevalent with carrier rates of 0.03-1.22%, while the sickle cell gene is variably distributed with carrier rates of 0.06-1.2%. Other structural hemoglobinopathies and δβ-thalassemia are sporadic. Twenty-seven different β-thalassemia mutations were identified, with seven constituting 82% of 1039 chromosomes characterized, namely: IVS-II-1 (G>A), IVS-I-6 (T>C), IVS-I-I (G>A), codon 8 (−AA), codon 8/9 (+G), IVS-I-110 (G>A), and codon 5 (-CT). There were notable regional variations in the distribution of β-thalassemia mutations, with Cd44 being mainly prevalent in the North, while IVS-I-110 is mainly prevalent in the East. In relevance to α-thalassemia, ten different mutations were detected, with the four most frequent constituting 92.4% of 262 alleles characterized being: −α 3.7 , -MED , α −5nt α, and α PolyA1 α. In relevance to sickle cell gene, it is seen in the northern part of the region bordering Turkey, with comparable prevalence rates, and is associated, similar to Turkey, mainly with the Benin haplotype, unlike that in Southern Iraq where it is associated with the Arab-Indian haplotype, similar to Eastern Arabian Peninsula. Given the high prevalence of hemoglobinopathies in the region, and the high rates of consanguineous marriages, a preventive program was initiated in 2008, and results of its first 5 years were promising, though there are still many outstanding challenges that require addressing.

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The association of HBG2, BCL11A, and HMIP polymorphisms with fetal hemoglobin and clinical phenotype in Iraqi Kurds with sickle cell disease

Abstract: It was demonstrated that SNPs in all three major HbF QTLs contribute significantly to HbF and clinical variability in Iraqi Kurds with SCD and that the cumulative number of minor alleles at contributing SNPs may serve as a better predictor of such variability in this population.

Cited by 9 publications

References 40 publications

Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea

Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea

Protocol for “Genetic composition of sickle cell disease in the Arab population: A systematic review”

Genetic epidemiology of hemoglobinopathies among Iraqi Kurds

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