Modulatory effect of single nucleotide polymorphism in Xmn1, BCL11A and HBS1L-MYB loci on fetal hemoglobin levels in ?-thalassemia major and Intermedia patients

Bashir, Shabnam; Mahmood, Saqib; Mohsin, Shahida; Tabassum, Iqra; Ghafoor, Mahmood; Sajjad, Osheen

doi:10.47391/jpma.1351

Cited by 5 publications

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“…One of the studies conducted in Pakistan, investigated modulatory effects of SNPs in Xmn1, BCL11A and HBS1L-MYB genes in β-Thalassemia major and intermedia patients and found an association. 11 The specific BCL11A polymorphism that they investigated was (rs766432).…”

Section: Discussionmentioning

confidence: 99%

Responses of β-thalassemia and compound heterozygote of Sickle/βthalassemia of BCL11A Gene Polymorphism in Pakistani Patients

Soomro,

Wahid,

Mehmood

et al. 2023

Pak J Med Sci

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Background and Objective: Beta-thalassemia major (β-Thal) and compound heterozygote of Sickle β-thalassemia (S-β Thal) are hereditary autosomal recessive disorders resulting from mutations or deletion in β-globin gene cluster. Patients with increased HbF levels having polymorphism at BCL11A site loci have shown clinical significance. The present study aimed to assess the frequency of BCL11A gene polymorphism in a study population of β-Thal, S-β Thal & Controls using Sanger sequencing leading to plot the HbF response of polymorphism with reference to wild type. Methods: The sample size of the study is n=180, groups were divided in Controls, β-thal & S-β thal. One ml blood was drawn from patients and controls to extract DNA for PCR amplification and BCL11A locus genotyping using Sanger sequencing. This study was carried out at Dow Research Institute of Biotechnology and Biomedical Sciences, for one year from March 2021 to February 2022. Results: The HbF response of three groups is hyperbolic with 83 for β-Thal, 16 for S-β Thal and close to zero for controls. The frequency of heterozygous variant GA of BCL11A gene polymorphism is 51%. The frequency of homozygous variant GG is 49%. Complete absence of wild type AA in patient group. The frequency of BCL11A polymorphism in control group was 43% (with male 18% and female 21%) showing wild type status of 57%. Conclusions: The patient groups of SCD and Beta thalassemia are devoid of wild type status. The wild type status of BCL11A is 57% even in control population. Higher level of HbF in B-thalassemia and SCD and B Thalassemia is a cost-effective screening marker before switching to an expensive genotyping testing. doi: https://doi.org/10.12669/pjms.39.6.7183 How to cite this: Soomro N, Wahid M, Mehmood M, Danish SH. Responses of β-thalassemia and compound heterozygote of Sickle/βthalassemia of BCL11A Gene Polymorphism in Pakistani Patients. Pak J Med Sci. 2023;39(6):---------. doi: https://doi.org/10.12669/pjms.39.6.7183 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Section: Discussionmentioning

confidence: 99%

Responses of β-thalassemia and compound heterozygote of Sickle/βthalassemia of BCL11A Gene Polymorphism in Pakistani Patients

Soomro,

Wahid,

Mehmood

et al. 2023

Pak J Med Sci

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“…Several reports concurrently demonstrate that the response to HbF inducers might depend on HbF-associated polymorphisms (e.g., HBG2 XmnI, BCL11A, and MYB polymorphisms) [93,94], and patient stratification based on these genetic characteristics might be useful for clinical management and the choice of the therapeutic protocol. For instance, Roy et al studied the influence of BCL11A, HBS1L-MYB, and HBBP1 single nucleotide polymorphisms (in addition to the HBG2 XmnI polymorphism) on the levels of endogenous production of HbF and found a significant association of HbF levels with rs2071348 (BCL11A) and rs4895441 (HBS1L-MYB), respectively.…”

Section: Major Dna Polymorphisms Associated With High Expression Of γ...mentioning

confidence: 99%

“…For instance, Roy et al studied the influence of BCL11A, HBS1L-MYB, and HBBP1 single nucleotide polymorphisms (in addition to the HBG2 XmnI polymorphism) on the levels of endogenous production of HbF and found a significant association of HbF levels with rs2071348 (BCL11A) and rs4895441 (HBS1L-MYB), respectively. The HBG2 XmnI polymorphism showed the strongest association [76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95]. An extensive description of SNPs associated with high production of HbF is outside the objectives of the present review that is mainly focused on the most relevant (in our opinion) DNA polymorphisms considered in published pharmacogenomic studies on β-thalassemia and SCD.…”

Section: Major Dna Polymorphisms Associated With High Expression Of γ...mentioning

confidence: 99%

Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications

Gambari,

Waziri,

Goonasekera

et al. 2024

IJMS

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In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of β-thalassemia or Sickle-cell disease (SCD). This field of investigation is relevant, since it is expected to help clinicians select the appropriate drug and the correct dosage for each patient. We first discussed the search for DNA polymorphisms associated with a high expression of γ-globin genes and identified this using GWAS studies and CRISPR-based gene editing approaches. We then presented validated DNA polymorphisms associated with a high HbF production (including, but not limited to the HBG2 XmnI polymorphism and those related to the BCL11A, MYB, KLF-1, and LYAR genes). The expression of microRNAs involved in the regulation of γ-globin genes was also presented in the context of pharmacomiRNomics. Then, the pharmacogenomics of validated fetal hemoglobin inducers (hydroxyurea, butyrate and butyrate analogues, thalidomide, and sirolimus), of iron chelators, and of analgesics in the pain management of SCD patients were considered. Finally, we discuss current clinical trials, as well as international research networks focusing on clinical issues related to pharmacogenomics in hematological diseases.

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“…Xmn1 polymorphism: The presence of G to T substitution at À158 position 5 0 to Gγ gene (Xmn1 polymorphism) is known to be associated with increased HbF production. Earlier investigations showed that patients with the Xmn1 (+/+) genotype were identified only in mildly affected patients; in contrast, patients having the Xmn1 (À/À) genotype exhibited severe phenotypes including early age of onset and more transfusion dependency [41,42]. Overall homozygosity for Xmn1 appeared as a crucial genetic determinants for HbE/β-thalassemia; although some conflicting data were presented.…”

Section: Determining Factors For Regulating Increased Hbf Levelmentioning

confidence: 99%

The Key Genetic Determinants Behind the Phenotypic Heterogeneity of HbE/β-thalassemia Patients and the Probable Management Strategy

Panja¹,

Das²,

Dolai³

et al. 2023

Thalassemia Syndromes - New Insights and Transfusion Modalities

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HbE/β-thalassemia is the most common severe form of thalassemia which is very prominent in South East Asian countries. It is responsible for nearly one-half of all the severe types of β-thalassemia all over the world. It is also known to represent a wide range of phenotypic diversity which varies from asymptomatic to transfusion-dependent severe phenotype. The most important predictive factor is mutations within the beta-globin gene (HBB). Apart from the primary genetic modifiers, there are certain other determinants regulating the phenotypic heterogeneity including, co-inheritance of alpha thalassemia mutations and other secondary modifiers including Xmn1 polymorphism, HBS1L-MYB, GATA-1, BCL11A polymorphism, and presence of HPFH mutations. Although the degree of severity is also determined by other tertiary genetic modifiers like increase in serum erythropoietin due to anemia, previous infection with malaria, environmental factors, splenectomy, etc. This review aimed to reveal the potential genetic predictors of HbE/β-thalassemia patients and the probable management strategy. This also enhances the generation of “personalized medicine” for better patient care. The instability of clinical phenotype and remarkable variation indicate careful monitoring of treatment for each patient and the therapeutic approaches should be monitored over time.

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Modulatory effect of single nucleotide polymorphism in Xmn1, BCL11A and HBS1L-MYB loci on fetal hemoglobin levels in ?-thalassemia major and Intermedia patients

Cited by 5 publications

References 0 publications

Responses of β-thalassemia and compound heterozygote of Sickle/βthalassemia of BCL11A Gene Polymorphism in Pakistani Patients

Responses of β-thalassemia and compound heterozygote of Sickle/βthalassemia of BCL11A Gene Polymorphism in Pakistani Patients

Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications

The Key Genetic Determinants Behind the Phenotypic Heterogeneity of HbE/β-thalassemia Patients and the Probable Management Strategy

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