HbF production in β thalassaemia heterozygotes for the IVS-II-1 G→A β0-globin mutation. Implication of the haplotype and theGγ-158 C→T mutation on the HbF level

Dedoussis, George; Mandilara, Georgia; Boussiu, Marina; Loutradis, Aphrodite

doi:10.1002/1096-8652(200007)64:3<151::aid-ajh2>3.0.co;2-x

Cited by 23 publications

(8 citation statements)

References 30 publications

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“…The association of some β-globin mutations with X mn 1 site with elevated HbF expression has been previously published. The role of increased HbF response as an ameliorating factor has become evident in patients who were mildly affected despite being homozygotes or compound heterozygotes for β 0 or β + thalassaemia 19. Association of X mn 1 and frequency of blood transfusion was reported in thalassemic patients 20, 21…”

Section: Discussionmentioning

confidence: 99%

Modulating Effect of the −158 Gγ (C→t) XMN-1 Polymorphism in Indian Sickle Cell Patients

Pandey

Mishra

et al. 2012

Mediterr J Hematol Infect Dis

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Xmn1 polymorphism is a known factor, which increases fetal haemoglobin production. Among the inherited disorders of blood, thalassaemia and Sickle Cell Diseases contributes to a major bulk of genetic diseases in India. Our aim was to verify the role of the Xmn1 polymorphism as a modulating factor in sickle cell patients and frequency of the polymorphism in Indian sickle cell patients. 60 sickle homozygous and 75 sickle beta thalassemia patients were included and 5 ml blood sample was collected from them. Screening of sickle patients was done by HPLC. An automated cell analyzer SYSMEX (K-4500 Model) was used to analyze the Complete Blood Count of patients. Xmn1 polymorphism analysis was done by PCR-RFLP and one-way ANOVA test was applied to analysis of variance between groups. Among the sickle patients 27 were heterozygous (+/−) and 19 were homozygous (+/+) while 30 were heterozygous (+/−) and 24 were homozygous (+/+) in sickle β-thalassemia patients. Extremely significant differences (p-value <0.001) of hematological parameters seen among patients with Xmn1 carrier and without the Xmn1 carrier. In our cases the clinical symptoms were barely visible and higher HbF level with Xmn1 carriers were found. Presence of Xmn1 polymorphism in sickle cell patients with higher HbF were phenotypically distinguished in the sickle cell patients. We conclude that the phenotypes of Indian sickle cell patients were greatly influenced by Xmn1polymorphism.

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Section: Discussionmentioning

confidence: 99%

Modulating Effect of the −158 Gγ (C→t) XMN-1 Polymorphism in Indian Sickle Cell Patients

Pandey

Mishra

et al. 2012

Mediterr J Hematol Infect Dis

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“…The interest in rapamycin-inducing HbF increase is related to the fact that this effect is not associated with cytotoxicity and cell growth inhibition, in contrast to effects observed with several other inducers (20,24). Further experiments are required in order to determine whether the extent of rapamycin-mediated enhancement of c-globin mRNA is associated with XmnI polymorphism, as elsewhere described (25,26).…”

Section: Discussionmentioning

confidence: 99%

Effects of rapamycin on accumulation of α‐, β‐ and γ‐globin mRNAs in erythroid precursor cells from β‐thalassaemia patients

Fibach

Bianchi

Borgatti

et al. 2006

European J of Haematology

116

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We studied the effects of rapamycin on cultures of erythroid progenitors derived from the peripheral blood of 10 beta-thalassaemia patients differing widely with respect to their potential to produce foetal haemoglobin (HbF). For this, we employed the two-phase liquid culture procedure for growing erythroid progenitors, high performance liquid chromatography for analysis of HbF production and reverse transcription polymerase chain reaction for quantification of the accumulation of globin mRNAs. The results demonstrated that rapamycin induced an increase of HbF in cultures from all the beta-thalassaemia patients studied and an increase of their overall Hb content/cell. The inducing effect of rapamycin was restricted to gamma-globin mRNA accumulation, being only minor for beta-globin and none for alpha-globin mRNAs. The ability of rapamycin to preferentially increase gamma-globin mRNA content and production of HbF in erythroid precursor cells from beta-thalassaemia patients is of great importance as this agent (also known as sirolimus or rapamune) is already in clinical use as an anti-rejection agent following kidney transplantation. These data suggest that rapamycin warrants further evaluation as a potential therapeutic drug in beta-thalassaemia and sickle cell anaemia.

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“…[ 15 ] Similarly, IVS-II-1 was highly associated with Xmn I polymorphism in Greek carriers. [ 28 ] Furthermore, IVS-II-1 was quite frequently associated with Xmn I in an earlier study on thalassemia intermedia in our region. [ 6 ]…”

Section: Discussionmentioning

confidence: 68%

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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HbF production in β thalassaemia heterozygotes for the IVS-II-1 G→A β0-globin mutation. Implication of the haplotype and theGγ-158 C→T mutation on the HbF level

Cited by 23 publications

References 30 publications

Modulating Effect of the −158 Gγ (C→t) XMN-1 Polymorphism in Indian Sickle Cell Patients

Modulating Effect of the −158 Gγ (C→t) XMN-1 Polymorphism in Indian Sickle Cell Patients

Effects of rapamycin on accumulation of α‐, β‐ and γ‐globin mRNAs in erythroid precursor cells from β‐thalassaemia patients

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

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