Xmn I polymorphism in Egyptian patients with β-thalassemia major and its correlation with the HbF level

Gawhary, Somaya El; Farid, Mona A.; Ezzat, Mostafa; ElAwady, Heba; Mostafa, Hisham

doi:10.1016/j.genrep.2018.02.005

Cited by 1 publication

(2 citation statements)

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“…The association between HbF levels and polymorphisms presented by SNPs in BCL11A gene and the Xmn1 gene has been demonstrated in different populations. 11 , 16 , 25–27 , 29–35 While HbF regulation is highly diversified and genetically controlled, reproducing association studies across different populations, particularly of diverse genetic backgrounds and environmental setting is likely to produce different observations in different studies. Interestingly, we observed a slightly reduced Hb level in the HU+ group and speculate that, this could be due to crenation and subsequent lysing of RBC’s since HU plays a role in RBC differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…SNPs were genotyped using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) as previously described. 11 , 13 The amplification process was performed using the BIO-RAD icycler thermal cycler (Bio-Rad, USA). RFLP analysis was carried out using AvaII, MboII, AatII and Xmn1 restriction enzymes (New England Biolabs, USA) for rs11886868, rs7606173 and rs6706648 and Xmn1, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Association Between Selected Single Nucleotide Polymorphisms in Globin and Related Genes and Response to Hydroxyurea Therapy in Ghanaian Children with Sickle Cell Disease

Manu

Segbefia

N’guessan

et al. 2022

PGPM

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Background Sickle cell disease (SCD) is a group of genetic disorders affecting the structure and function of haemoglobin. Hydroxyurea (HU) stimulates fetal haemoglobin (HbF) and reduces sickle erythrocyte-endothelial cell interaction. However, the degree of HbF response to HU varies, with HbF expression-associated single nucleotide polymorphisms (SNPs) in quantitative trait loci (QTL) been implicated. We investigated the relationship between four SNPs (rs11886868, rs6706648, rs7606173 and 158C/T Xmn1) in two QTL (B-cell lymphoma 11A (BCL11A) and Xmn1) and HbF levels in children with SCD in Accra, Ghana. Methods A total of 110 children with SCD in steady-state, comprising 64 and 46 SCD children treated with HU (HU+) or with no history of HU therapy (HU-), respectively, were recruited. HbF levels were measured in peripheral blood by alkali denaturation and SNPs were genotyped using polymerase chain reaction and restriction fragment length polymorphism. Results The presence of SNPs (rs11886868, rs6706648, rs7606173 and −158C/T Xmn1) was identified. Observed heterozygosity and homozygosity for the derived alleles were 45.7%, 82.6%, 21.7% and 39.1% in rs11886868, rs6706648, rs7606173 and −158C/T Xmn1 polymorphisms, respectively, for the HU+ population. Observed frequencies of the minor alleles were 0.204, 0.477, 0.171 and 0.190 for rs11886868, rs6706648, rs7606173 and −158C/T Xmn1 polymorphisms, respectively. The three BCL11A SNPs in the HU+ population showed homozygous individuals for rs11886868 (CC), rs6706648 (CC) and heterozygous or homozygous mutant individuals for rs7606173 (CG/GG) having higher HbF values. The combined effect of the SNPs was associated with variance in HbF levels in the HU+ population. The BCL11A SNP, rs6706648 was strongly associated with HbF levels and the C allele frequency, with significantly elevated HbF levels. Conclusion An association between the various variants and combined effect of SNPs and HbF among children with SCD was found and confirms the known association between HU intake and increased HbF in SCD.

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