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ISSN: 1734-1922
Archives of Medical Science
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1/2018
vol. 14
 
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abstract:
Basic research

KLF1 gene and borderline hemoglobin A2 in Saudi population

J. Francis Borgio, Sayed AbdulAzeez, Ahmed M. Al-Muslami, Zaki A. Naserullah, Sana Al-Jarrash, Ahmed M. Al-Suliman, Mohammed S. Al-Madan, Amein K. Al-Ali

Arch Med Sci 2018; 14, 1: 230–236
Online publish date: 2017/12/19
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Introduction: Elevated HbA2 (hemoglobin A2) level is considered the most reliable hematological parameter for the detection of β-thalassemia carriers. However, some carriers are difficult to recognize because the level of HbA2 is not in the distinctive carrier range, i.e. 4.0–6.0%; instead, some carriers have HbA2 levels between normal and carrier levels, i.e. borderline HbA2 (HbA2 = 3.1–3.9%). Studies have shown that variations in the erythroid Krüppel-like factor (KLF1) gene lead to borderline HbA2 in β-thalassemia carriers from various populations. The incidence of borderline HbA2 in Saudis is high.

Material and methods: To confirm the influence of variations in KLF1, HBA1, HBA2 and HBB genes for the reduction of the level of HbA2 in Saudi β-thalassemia carriers, we performed a direct sequence analysis of KLF1, HBA1, HBA2 and HBB genes from 212 healthy Saudis (88 subjects: HbA2 < 3; 72 subjects: HbA2 = 3.1 to 3.9; 52 subjects HbA2 > 4.3).

Results: The presence of the borderline HbA2 level is not specific to any type of β-thalassemia variation or β+-thalassemia variations in Saudis. Two exonic (c.304T>C and c.544T>C) and two 3 untranslated region (3UTR) (c.*296G>A and c.*277C>G) variations have been identified in the KLF1 gene for the first time from an Arab population. None of these four variations in KLF1 genes are significantly associated with the Saudis with borderline HbA2. α Globin genotype, –α23.71α2, is found to be the most frequent (55.55%) among healthy Saudis with borderline HbA2 compared with the other groups (HbA2 < 3 = 20.45%; HbA2 > 4.3 = 13.51%).

Conclusions: Further studies are necessary to determine the influence of other factors on the presence of borderline HbA2 in 41.67% of Saudis.
keywords:

β-thalassemia carrier, borderline HbA2, KLF1 gene, Saudi Arabia, variations, HBB gene, HBA1 gene, HBA2 gene

references:
Harteveld CL, Higgs DR. Alpha-thalassaemia. Orphanet J Rare Dis 2010; 5: 13.
Akhtar MS, Qaw F, Borgio JF. Spectrum of alpha-thalassemia mutations in transfusion-dependent beta-thalassemia patients from the Eastern Province of Saudi Arabia. Hemoglobin 2013; 37: 65-73.
Hamamy HA, Al-Allawi NA, Epidemiological profile of common haemoglobinopathies in Arab countries.
J Community Genet 2013; 4: 147-67.
Borgio JF. Molecular nature of alpha-globin genes in the Saudi population. Saudi Med J 2015; 36: 1271-6.
Borgio JF, AbdulAzeez S, Naserullah ZA, et al. Mutations in the beta-globin gene from a Saudi population: an update. Int J Lab Hematol 2016; 38: e38.
Al-Nafie AN, Borgio JF, AbdulAzeez S, et al. Co-inheritance of novel ATRX gene mutation and globin (alpha & beta) gene mutations in transfusion dependent beta-thalassemia patients. Blood Cells Mol Dis 2015; 55: 27-9.
Mosca A, Paleari R, Galanello R, et al. IFCC Working Group on Standardization of HbA2. New analytical tools and epidemiological data for the identification of HbA2 borderline subjects in the screening for beta-thalassemia. Bioelectrochemistry 2008; 73: 137-40.
Giambona A, Passarello C, Vinciguerra M, et al. Significance of borderline hemoglobin A2 values in an Italian population with a high prevalence of beta-thalassemia. Haematologica 2008; 93: 1380-4.
Perseu L, Satta S, Moi P, et al. KLF1 gene mutations cause borderline HbA2. Blood 2011; 118: 4454-8.
Tallack MR, Perkins AC, Three fingers on the switch: Krüppel-like factor 1 regulation of gamma-globin to beta-globin gene switching. Curr Opin Hematol 2013; 20: 193-200.
Love PE, Warzecha C, Li L. Ldb1 complexes: the new master regulators of erythroid gene transcription. Trends Genet 2014; 30: 1-9.
Singleton BK, Burton NM, Green C, et al. Mutations in EKLF/KLF1 form the molecular basis of the rare blood group In (Lu) phenotype. Blood 2008; 112: 2081-8.
Borgio JF, AbdulAzeez S, Al-Nafie AN, et al. A novel HBA2 gene conversion in cis or trans: “2 allele” in a Saudi population. Blood Cells Mol Dis 2014; 53: 199-203.
Gaspar P, Lopes P, Oliveira J, et al. Variobox: automatic detection and annotation of human genetic variants. Hum Mutat 2014; 35: 202-7.
Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 2013; 30: 772-80.
AbdulAzeez Sayed, Francis Borgio J. In-Silico computing of the most deleterious nsSNPs in HBA1 gene. PloS One 2016; 11: e0147702.
Borgio JF, Al-Madan MS, AbdulAzeez S. Mutation near the binding interfaces at alpha-hemoglobin stabilizing protein is highly pathogenic. Am J Transl Res 2016; 8: 4224-32.
Kiefer F, Arnold K, Künzli M, et al. The SWISS-MODEL Repository and associated resources. Nucl Acids Res 2009; 37: D387-92.
Berman HM, Westbrook J, Feng Z. The protein data bank. Nucleic Acids Res 2000; 28: 235-42.
Feng L, Gell DA, Zhou S, et al. Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin. Cell 2004; 119: 629-40.
Laskowski RA, MacArthur MW, Moss DS, et al. PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 1993; 26: 283-91.
Satta S, Perseu L, Moi P, et al. Compound heterozygosity for KLF1 mutations associated with remarkable increase of fetal hemoglobin and red cell protoporphyrin. Haematologica 2011; 96: 767-70.
Satta S, Perseu L, Maccioni L, et al. Delayed fetal hemoglobin switching in subjects with KLF1 gene mutation. Blood Cells Mol Dis 2012; 48: 22-4.
Liu D, Zhang X, Yu L, et al. KLF1 mutations are relatively more common in a thalassemia endemic region and ameliorate the severity of beta-thalassemia. Blood 2014; 124: 803-11.
Yu LH, Liu D, Cai R, et al. Changes in hematological parameters in alpha-thalassemia individuals co-inherited with erythroid Krüppel-like factor mutations. Clin Genet 2015; 88: 56-61.
Al-Asmary SM, Kadasah S, Arfin M, et al. Apolipoprotein E polymorphism is associated with susceptibility to schizophrenia among Saudis. Arch Med Sci 2015; 11: 869-76.
Guvenc B, Canataroglu A, Unsal C, et al. Beta-globin chain abnormalities with coexisting alpha-thalassemia mutations. Arch Med Sci 2012; 8: 644-9.
Okuturlar Y, Gedikbasi A, Akalin N, et al. Serum paraoxonase 1 activity in patients with iron deficiency anemia. Arch Med Sci 2016; 12: 697-703.
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