Frequency of Gγ-globin promoter −158 (C&gt;T) XmnI polymorphism in patients with homozygous/compound heterozygous beta thalassaemia

Ali, Nadir; Ayyub, Muhammad; Khan, Saleem Ahmed; Ahmed, Suhaib; Abbas, Kazim; Malik, Hamid Saeed; Tashfeen, Sunila

doi:10.1016/j.hemonc.2014.12.004

Cited by 16 publications

(13 citation statements)

References 20 publications

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“…The latter findings are consistent with earlier reports that the Xmn I SNP is the commonest ameliorating factor in cases with β° mutations but not β + [4, 37]. However, in our study the percentage of TI patients having the Xmn I SNP was low, in consistency with an earlier report from Brazil (9.7%) [38] but inconsistent to previous reports from Iraq (56.8%) [4], Iran (51.9%), [28] Pakistan (23%) [14] and China (26.5%) [39].…”

Section: Discussioncontrasting

confidence: 57%

“…Analysis of the Gγ-globin gene Xmn I SNP showed that three patients were homozygous and one patient was heterozygous for this SNP, three of them have the β 0 /β 0 genotype and one has the β 0 /β + (in addition to –α 3.7 / αα) and the effect of this SNP was clearly illustrated by the high levels of HbF in these patients. The role of Gγ-globin gene Xmn I SNP in increasing HbF levels and moderation of thalassemia phenotype is widely known and reported in many earlier studies [4, 14, 35]. The Xmn I polymorphism is one of three major HbF quantitative trait loci (QTLs) responsible for HbF variation, and it leads to a less severe phenotype by increasing γ-chain production, which helps to neutralize unbounded α-chains [15, 36].…”

Section: Discussionmentioning

confidence: 99%

“…The XmnI SNP (− 158 C > T) at the 5’end of Gγ-globin gene was detected using RFLP-PCR using the primer pair: Forward primer (5′- AAC TGT TGC TTT ATA GGA TTT-3′) and Reverse primer (5′- TTT TAT TCT TCA TCC CTA GC-3′). The forward primer was described earlier by [14]. Digestion of the PCR product (592 bp) with XmnI allowed the differentiation of three possible genotypes: the T/T or −/− (592 bp); C/T or −/+ (592, 445, 147 bp); and C/C or +/+ genotype (445 and 147 bp).…”

Section: Methodsmentioning

confidence: 99%

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Molecular characterization of β-thalassemia intermedia in the West Bank, Palestine

Faraon

Daraghmah²,

Samarah

et al. 2019

BMC Hematol

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Background We aimed to investigate the molecular basis of β-Thalassemia intermedia (TI) in the West Bank region and its management practices. Methods This was a case series multi-center study and included 51 cases of TI. DNA sequencing was used to analyze β-globin gene mutations. Common α-globin gene mutations were screened by Gap-PCR (−α 3.7 , −α 4.2 , −- MED , ααα anti3.7 ) or DNA sequencing (α2-IVS II 5 nt del). Xmn I -158 C > T polymorphisms of Gγ-globin gene was determined by RFLP-PCR. Results Seven β-globin gene mutations were observed, namely IVS-I -6 C > T, IVS-I-110 G > A, IVS-II-1 G > A, IVS-I-1 G > A, Codon 37 Trp > Stop, beta − 101 and IVS-II-848 C > A. Ten genotypes were observed. Homozygosity for IVS-I-6 accounted for the majority of TI cases with a frequency of 74.5%. The second common β-globin gene genotype was homozygote IVS-I-110 G > A (5.8%) and homozygote IVS-II-1 G > A (5.8%). The remaining seven genotypes were each detected in about 2% of patients. α-Thalassemia mutations were seen in five patients (9.8%), and included (−α 3.7 , ααα anti3.7 and α2-IVSII-5 nt del). Xmn I polymorphism was observed in four patients (7.8%), three homozygotes and one heterozygote. Conclusions Homozygosity for the mild β-globin gene IVS-I-6 allele was the major contributing factor for the TI phenotype among the study subjects. The role of Xmn I SNP and α-thalassemia mutations in ameliorating the TI phenotype was observed in few patients for each factor. The beta − 101 C > T mutation was diagnosed in one patient in homozygote state for the first time in Palestine.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Molecular characterization of β-thalassemia intermedia in the West Bank, Palestine

Faraon

Daraghmah²,

Samarah

et al. 2019

BMC Hematol

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“…A study in Pakistan reported that a minor allele in the XmnI locus has a frequency of 23-36% [31], whereas this was reported to be 16% [32] and 8% [33] in Indian and Malay populations, respectively. In accordance with the data from the HapMap project (updated 2012), the rs11886868 genotype has a wide distribution that varies in populations throughout the world.…”

Section: Relationship Between Snps Distribution and Clinical Appearancementioning

confidence: 99%

Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances: A study on β-thalassemia and hemoglobin E/β-thalassemia patients in Indonesia

Rujito

Basalamah²,

Siswandari

et al. 2016

Hematology/Oncology and Stem Cell Therapy

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“…Studies on β-thal carriers from Brazil, Northern Pakistan, Turkey, and Hong Kong reported rates of 0.19, 0.16, 0.18, and 0.07, respectively. [ 23 24 25 26 ] These rates may be relevant to the underlying β-thal genotypes in these populations. Although the current study did not include molecular characterization of the underlying β-genotypes, earlier studies have documented that IVS-II-1 (G>A), codon 44 (-G), codon 5 (-CT), IVS-I-1 (G>A), and codon 39 (C>T) are the five most common β-thal mutants in carriers from our region.…”

Section: Discussionmentioning

confidence: 99%

HBG2 -158 (C>T) polymorphism and its contribution to fetal hemoglobin variability in Iraqi Kurds with beta-thalassemia minor

2018

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PURPOSE: Hemoglobin (Hb) F% is increased in up to half of beta-thalassemia (β-thal) carriers. Several polymorphisms have been linked to such variability in different populations, including HBG2 - 158(C>T) (Xmn I polymorphism) on chromosome 11. To determine the role of this polymorphism in such variability among Iraqi Kurds, the current study was initiated. MATERIALS AND METHODS: A total of 102 consecutive patients diagnosed as β-thal minor were enrolled. The enrollees had their diagnosis based on peripheral blood counts and high-performance liquid chromatography to determine HbA2 and HbF. All enrollees had their DNA extracted by phenol-chloroform method and Xmn I polymorphism detected by restriction fragment length polymorphism-polymerase chain reaction. RESULTS: The mean age (standard deviation [SD]) of the 102 enrollees was 25.4 (14.0) years, and the enrollees included 48 males and 54 females. Xmn I polymorphism was identified in heterozygous state in 46 (45.1%) patients and in homozygous state in one patient (0.98%). Thus, the minor allele frequency of this polymorphism was 0.235 in the studied group. There were no significant differences in red cell indices and HbA2% in carriers of the minor allele compared to noncarriers, while HbF% and absolute HbF concentrations were significantly higher in the former subgroup (P = 0.032 and 0.014, respectively). This polymorphism's contribution to HbF variability was found to be 5.8% in the studied sample. Furthermore, those with HbF ≥2% were 3.2 folds more likely to carry the minor allele. CONCLUSIONS: Xmn I polymorphism is frequently encountered in Iraqi Kurds with β-thal minor, and it is significantly associated with higher fetal hemoglobin in these patients.

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Frequency of Gγ-globin promoter −158 (C>T) XmnI polymorphism in patients with homozygous/compound heterozygous beta thalassaemia

Abstract: XmnI polymorphism in homozygous/compound heterozygous BT group is 13%. The most common genotype associated with XmnI polymorphism was IVSI-5/IVSI-5.

Cited by 16 publications

References 20 publications

Molecular characterization of β-thalassemia intermedia in the West Bank, Palestine

Molecular characterization of β-thalassemia intermedia in the West Bank, Palestine

Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances: A study on β-thalassemia and hemoglobin E/β-thalassemia patients in Indonesia

HBG2 -158 (C>T) polymorphism and its contribution to fetal hemoglobin variability in Iraqi Kurds with beta-thalassemia minor

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