Detection of single nucleotide polymorphisms in acquired anemia patients with high hemoglobin f
Anemia is a common clinical condition that can be either acquired or inherited. Normally, adults display fetal hemoglobin (HbF) levels of <1%, but variability in genomic regions can cause higher HbF levels (>1%). Unlike inherited anemia, clinical and genetic data on HbF levels associated wi...
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| Format: | Thesis |
| Language: | English |
| Published: |
2024
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| Subjects: | |
| Online Access: | http://eprints.usm.my/60998/1/SITI%20NUR%20NABEELA%20A%27IFAH%20BINTI%20MOHAMMAD-FINAL%20THESIS%20P-UM000420%28R%29-E.pdf |
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| Summary: | Anemia is a common clinical condition that can be either acquired or inherited.
Normally, adults display fetal hemoglobin (HbF) levels of <1%, but variability in
genomic regions can cause higher HbF levels (>1%). Unlike inherited anemia, clinical
and genetic data on HbF levels associated with acquired causes of anemia among the
Malaysian population are still scarce. Therefore, this study aims to determine the
association between HbF level and single nucleotide polymorphisms (SNPs) in
acquired anemia patients. A total of 106 out of 223 anaemic patients were detected to
have high HbF levels using high performance liquid chromatography (HPLC). From
106 patients with high HbF, 79 (74.5%) samples were found to have high HbA2
(=/>3.2%) and were tested with multiplex amplification refractory mutations-system
polymerase chain reactions (ARMS-PCR) for β-globin gene mutation while the
remaining 27 anemic patients with high HbF has lower HbA2 (<3.2%) were tested
using multiplex gap-PCR for four β-globin gene cluster deletion (Siriraj J Gγ(Aγδβ)othalassemia,
Thai (δβ)°-thalassaemia, HPFH-6, and Hb Lepore). β-globin gene
mutations were detected in 50 patients using multiplex ARMS-PCR, 37 heterozygous
Cd26, 6 heterozygous IVS 1-5, 3 heterozygous Cd 41/42, 1 heterozygous IVS 1-1, 2
compound heterozygous Cd26 with Cd8/9, and 1 compound heterozygous Cd26 with
Cd41/42. However, no β-globin gene cluster deletion detected in all 27 patients.
Besides, there was no significant difference between the HbF levels of acquired and
inherited anemic patients. 36 genomic DNA of samples with high HbF and no mutation
and deletion together with 5 DNA samples with normal HbF level were chosen for analysis using the Infinium Asian Screening SNPs microarray platform. Two SNPs,
rs73170684 and rs2893863 in GSTK1 and CDK1 gene were observed as the most
significant variants that achieved GWA significant threshold (p<10-8). However, other
SNPs from common major loci associated with high HbF, such as those in HBS1LMYB
and BCL11A genes, were not significant. Thus, these findings can be used as a
new genetic predictor and guideline for future studies in high HbF levels among
acquired anemic patients for better treatment. |
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