Hb F Levels in Indian Sickle Cell Patients and Association with the <i>HBB</i> Locus Variant rs10128556 (C&gt;T), and the <i>HBG Xmn</i>I (Arab-Indian) Variant

Bhanushali, Aparna A.; Kumari, Himani; Patra, Pradeep Kumar; Das, Bibhu Ranjan

doi:10.1080/03630269.2017.1414059

Cited by 7 publications

(4 citation statements)

References 14 publications

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“…This limitation should not affect our study, because (1) the AI haplotype has only been found in tribes in India and in population of the eastern part of Saudi Arabia, and most of our patients originate from Western and Central Africa. In addition, none of the published studies in SCD patients from Eastern Africa have reported the presence of the AI haplotype [51][52][53][54] ; and (2) the SEN and the AI haplotypes share the rs 7482144 C/T, which is the strongest predictor of HbF expression, and is located on chromosome 11, even in the AI group [55][56][57] In our study, G6PD deficiency was not defined by gene analysis but by abnormally low G6PD activity. As G6PD deficiency is caused by mutations in the X-linked G6PD gene, heterozygous females may have normal G6PD activity or be deficient.…”

Section: Discussioncontrasting

confidence: 61%

“…As G6PD deficiency is caused by mutations in the X-linked G6PD gene, heterozygous females may have normal G6PD activity or be deficient. 57 Thus, gene analysis does not allow detection of G6PD deficiency in heterozygous girls. Moreover, even if the G6PD A2 allele, which contains 2 mutations, G376A and G202A, is the most common G6PD deficiency variant in Africa, 160 mutations of the G6PD gene have been identified, [58][59][60][61] justifying that G6PD deficiency be detected by using methods measuring activity such as a spectrophotometric assay, provided that reticulocytosis is assessed and the comparison with hexokinase activity is done to control for the effects of cell age.…”

Section: Discussionmentioning

confidence: 99%

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Biological impact of α genes, β haplotypes, and G6PD activity in sickle cell anemia at baseline and with hydroxyurea

Bernaudin¹,

Kamdem²,

Hau

et al. 2018

Blood Advances

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Sickle cell anemia (SCA), albeit monogenic, has heterogeneous phenotypic expression, mainly related to the level of hemoglobin F (HbF). No large cohort studies have ever compared biological parameters in patients with major β-globin haplotypes; ie, Senegal (SEN), Benin (BEN), and Bantu/Central African Republic (CAR). The aim of this study was to evaluate the biological impact of α genes, β haplotypes, and glucose-6-phosphate dehydrogenase (G6PD) activity at baseline and with hydroxyurea (HU). Homozygous HbS patients from the Créteil pediatric cohort with available α-gene and β-haplotype data were included (n = 580; 301 females and 279 males) in this retrospective study. Homozygous β-haplotype patients represented 74% of cases (37.4% CAR/CAR, 24.3% BEN/BEN, and 12.1% SEN/SEN). HU was given to 168 cohort SCA children. Hematological parameters were recorded when HbF was maximal, and changes (HU-T0) were calculated. At baseline, CAR-haplotype and α-gene numbers were independently and negatively correlated with Hb and positively correlated with lactate dehydrogenase. HbF was negatively correlated with CAR-haplotype numbers and positively with BEN- and SEN-haplotype numbers. The /rs1427407 "T" allele, which is favorable for HbF expression, was positively correlated with BEN- and negatively correlated with CAR-haplotype numbers. With HU treatment, and HbF values were positively correlated with the BEN-haplotype number. BEN/BEN patients had higher HbF and Hb levels than CAR/CAR and SEN/SEN patients. In conclusion, we show that BEN/BEN patients have the best response on HU and suggest that this could be related to the higher prevalence of the favorable /rs1427407/T/allele for HbF expression in these patients.

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Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Biological impact of α genes, β haplotypes, and G6PD activity in sickle cell anemia at baseline and with hydroxyurea

Bernaudin¹,

Kamdem²,

Hau

et al. 2018

Blood Advances

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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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“…The three most important quantitative trait loci (QTLs) are C/T at position −158 of HBG2 on chromosome 11p15.4 termed Xmn1-HBG2 or rs7482144, the SNP located at the HBS1L-MYB intergenic region on chromosome 6q23 and the SNP located at the BCL11A gene on chromosome 2p16. [9][10][11] DNA polymorphisms at these three sites account for approximately 10%-50% of the variations in the levels of HbF, indicating that additional loci are also involved. 12,13 Many studies have shown that the HBG1-HBD intergenic region plays an important regulatory role in the process of γ to β-globin gene switch.…”

Section: Introductionmentioning

confidence: 99%

Association of polymorphisms in the HBG1‐HBD intergenic region with HbF levels

Huang

Han

et al. 2020

Clinical Laboratory Analysis

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Background: Increased levels of fetal hemoglobin (HbF) can improve the clinical course of the patients with sickle cell anemia (SCA) or β-thalassemia. The HBG1-HBD intergenic region plays an important role in this process. However, very few studies investigated whether the variations in this region have an effect on HbF expression. Methods:We retrieved all the SNP data in the HBG1-HBD intergenic region and defined the haplotype blocks, then performed cluster analysis and selected a tagSNP.A total of 500 normal individuals and 300 β-thalassemia carriers were enrolled. After routine blood and hemoglobin capillary electrophoresis testing, β-thalassemia mutations were detected using PCR-reverse dot blot. The genotypes of the rs4910736 (A > C) and rs10128556 (C > T) were determined using Sanger sequencing; the relationship between the two SNPs and the levels of HbF was analyzed.Results: Two haplotype blocks were constructed. Block 1 included seven haplotypes divided into two groups M and N by 11 tagSNPs, among which rs4910736 was selected as a tagSNP, while block 2 included three haplotypes. We found that the haplotypes of block 1 were statistically associated with HbF levels, but the non-tagSNP rs10128556 was shown to be more strongly associated with HbF levels than rs4910736. Conclusion:This work proved that the haplotypes in the HBG1-HBD intergenic region and SNP rs10128556 are both statistically associated with HbF levels, revealing the association of polymorphisms in the HBG1-HBD intergenic region with HbF levels.

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Hb F Levels in Indian Sickle Cell Patients and Association with the HBB Locus Variant rs10128556 (C>T), and the HBG XmnI (Arab-Indian) Variant

Cited by 7 publications

References 14 publications

Biological impact of α genes, β haplotypes, and G6PD activity in sickle cell anemia at baseline and with hydroxyurea

Biological impact of α genes, β haplotypes, and G6PD activity in sickle cell anemia at baseline and with hydroxyurea

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

Association of polymorphisms in the HBG1‐HBD intergenic region with HbF levels

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