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Research Article
Anita Nadkarni
National Institute of Immunohaematology
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Introduction:
Hemoglobinopathies though a monogenic disorder, show phenotypic variability. Hence, understanding the genetics underlying the heritable sub-phenotypes of hemoglobinopathies, specific to each population, would be prognostically useful and could inform personalized therapeutics. This study aimed to evaluate the role of genetic modifiers leading to higher HbF production with cumulative impact of the modifiers on disease severity.
Materials and methods:
200 patients [100 β-thalassemia homozygotes,100 Sickle Cell Anemia], and 50 healthy controls were recruited. Primary screening followed with molecular analysis for confirming the β-hemoglobinopathy was performed. Co-existing α-thalassemia and the polymorphisms located in 3 genetic loci linked to HbF regulation were screened.
Results:
The most remarkable result was the association of SNPs with clinically relevant phenotypic groups. The γ-globin gene promoter polymorphisms [-158 C→T,+25 G→A],BCL11A rs1427407 G→T,-3 bp HBS1L-MYB rs66650371 and rs9399137 T→C polymorphisms were correlated with higher HbF, in group that has lower disease severity score (P<0.00001), milder clinical presentation, and a significant delay in the age of the first transfusion.
Conclusion:
Our study emphasizes the complex genetic interactions underlying the disease phenotype that may be a prognostic marker for predicting the clinical severity and assist in disease management.
Keywords
Genetic modifiers, phenotypic variability, β-hemoglobinopathies
Figure 1
Figure 2
Figure 3
Figure 4
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
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Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 17 Mar, 2021
No community comments so far
Editorial decision: Major revision
On 21 Jul, 2021
Reviews received
Received 16 Jul, 2021
Reviewers agreed
On 25 Jun, 2021
Reviews received
Received 07 Apr, 2021
Reviewers agreed
On 28 Mar, 2021
Reviewers invited
Invitations sent on 27 Mar, 2021
Editor assigned
On 22 Mar, 2021
Editor invited
On 16 Mar, 2021
Submission checks complete
On 16 Mar, 2021
First submitted
On 28 Feb, 2021
Metrics
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HTML Views: ...
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Anita Nadkarni
National Institute of Immunohaematology
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 17 Mar, 2021
No community comments so far
Editorial decision: Major revision
On 21 Jul, 2021
Reviews received
Received 16 Jul, 2021
Reviewers agreed
On 25 Jun, 2021
Reviews received
Received 07 Apr, 2021
Reviewers agreed
On 28 Mar, 2021
Reviewers invited
Invitations sent on 27 Mar, 2021
Editor assigned
On 22 Mar, 2021
Editor invited
On 16 Mar, 2021
Submission checks complete
On 16 Mar, 2021
First submitted
On 28 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Introduction:
Hemoglobinopathies though a monogenic disorder, show phenotypic variability. Hence, understanding the genetics underlying the heritable sub-phenotypes of hemoglobinopathies, specific to each population, would be prognostically useful and could inform personalized therapeutics. This study aimed to evaluate the role of genetic modifiers leading to higher HbF production with cumulative impact of the modifiers on disease severity.
Materials and methods:
200 patients [100 β-thalassemia homozygotes,100 Sickle Cell Anemia], and 50 healthy controls were recruited. Primary screening followed with molecular analysis for confirming the β-hemoglobinopathy was performed. Co-existing α-thalassemia and the polymorphisms located in 3 genetic loci linked to HbF regulation were screened.
Results:
The most remarkable result was the association of SNPs with clinically relevant phenotypic groups. The γ-globin gene promoter polymorphisms [-158 C→T,+25 G→A],BCL11A rs1427407 G→T,-3 bp HBS1L-MYB rs66650371 and rs9399137 T→C polymorphisms were correlated with higher HbF, in group that has lower disease severity score (P<0.00001), milder clinical presentation, and a significant delay in the age of the first transfusion.
Conclusion:
Our study emphasizes the complex genetic interactions underlying the disease phenotype that may be a prognostic marker for predicting the clinical severity and assist in disease management.
Figure 1
Figure 2
Figure 3
Figure 4
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
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