Krüppel-like factor 1 (KLF1) gene single nucleotide polymorphisms in sickle cell disease and its association with disease-related morbidities.
Fetal hemoglobin
Krüppel-like factor 1
Morbidities
Sickle cell disease
Xmn-I polymorphism
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
07
09
2020
accepted:
16
12
2020
pubmed:
4
1
2021
medline:
27
1
2021
entrez:
3
1
2021
Statut:
ppublish
Résumé
Sickle cell disease has varied clinical symptoms, and patients having high fetal hemoglobin (HbF) have milder symptoms. Various genetic factors are known to modulate the HbF levels. Krüppel-like factor 1 (KLF1) is a transcription factor that regulates the beta-like globin gene expression. Any variation in KLF1 gene may alter the sickle cell disease phenotype. Xmn-I polymorphism is also known to regulate the gamma globin gene expression. Present studies were carried out to investigate the effect of KLF1 gene mutations and Xmn-I polymorphism on the sickle cell disease severity and to ascertain the genotype-phenotype correlation. One hundred and eighteen sickle cell disease patients having a median follow-up of 5 years (3-10 years) were recruited. Clinical details were recorded from their retrospective medical records. Xmn-I polymorphism were analyzed using PCR-RFLP method. Variations in KLF1 gene were identified using Sanger sequencing. Out of 118 patients, 24 had acute chest syndrome and 21 patients had more than 2 pain episodes per year. There were no significant differences in sickle cell disease-related morbidities in male and females barring leg ulcers. A total of 6 polymorphism were observed in KLF1 gene, out of which 3 are novel (c.-304G > C, c.*141A > G and c.*178A > G). No statistically significant association of any of SNPs identified in KLF1 gene or Xmn-I polymorphism was seen with HbF levels as well as the sickle cell disease-related morbidities. No association exists between fetal hemoglobin or sickle cell disease-related morbidities and Xmn-I polymorphism or with SNPs identified in KLF1 gene in the studied cohort.
Identifiants
pubmed: 33388857
doi: 10.1007/s00277-020-04381-z
pii: 10.1007/s00277-020-04381-z
doi:
Substances chimiques
Kruppel-Like Transcription Factors
0
erythroid Kruppel-like factor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
365-373Références
Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN (2013) Global burden of sickle cell anaemia in children under five, 2010-2050: modelling based on demographics, excess mortality, and interventions. PLoS Med 10:e1001484
doi: 10.1371/journal.pmed.1001484
Piel FB, Steinberg MH, Rees DC (2017) Sickle cell disease. N Engl J Med 376(16):1561–1573
doi: 10.1056/NEJMra1510865
Perkins A, Xu X, Higgs DR, Patrinos GP, Arnaud L, Bieker JJ, Philipsen S; KLF1 Consensus Workgroup (2016) Krüppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants. Blood 27(15):1856–1862
Zhou D, Liu K, Sun CW, Pawlik KM, Townes TM (2010) KLF1 regulates BCL11A expression and gamma- to beta-globin gene switching. Nat Genet 42(9):742–744
doi: 10.1038/ng.637
Miller IJ, Bieker JJ (1993) A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family of nuclear proteins. Mol Cell Biol 13(5):2776–2786
doi: 10.1128/MCB.13.5.2776
Satta S, Perseu L, Moi P, Asunis I, Cabriolu A, Maccioni L, Demartis FR, Manunza L, Cao A, Galanello R (2011) Compound heterozygosity for KLF1 mutations associated with remarkable increase of fetal hemoglobin and red cell protoporphyrin. Haematologica 96(5):767–770
doi: 10.3324/haematol.2010.037333
Radmilovic M, Zukic B, Petrovic MS, Bartsakoulia M, Stankovic B, Kotur N, Dokmanovic L, Georgitsi M, Patrinos GP, Pavlovic S (2013) Functional analysis of a novel KLF1 gene promoter variation associated with hereditary persistence of fetal hemoglobin. Ann Hematol 92(1):53–58
doi: 10.1007/s00277-012-1625-9
Tepakhan W, Yamsri S, Fucharoen G, Sanchaisuriya K, Fucharoen S (2015) Krüppel-like factor 1 mutations and expression of hemoglobins F and A2 in homozygous hemoglobin E syndrome. Ann Hematol 94(7):1093–1098
doi: 10.1007/s00277-015-2335-x
Borg J, Papadopoulos P, Georgitsi M, Gutiérrez L, Grech G, Fanis P, Phylactides M, Verkerk AJMH, van der Spek PJ, Scerri CA, Cassar W, Galdies R, van IJcken W, Özgür Z, Gillemans N, Hou J, Bugeja M, Grosveld FG, von Lindern M, Felice AE, Patrinos GP, Philipsen S (2010) Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin. Nat Genet 42(9):801–805
doi: 10.1038/ng.630
Perkins AC, Sharpe AH, Orkin SH (1995) Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF. Nature 375(6529):318–322
doi: 10.1038/375318a0
Nitta T, Kawano F, Yamashiro Y, Takagi F, Murata T, Tanaka T, Ferania M, Adhiyanto C, Hattori Y (2015) A new Krüppel-like factor 1 mutation (c.947G > a or p.C316Y) in humans causes β-thalassemia minor. Hemoglobin 39(2):121–126
doi: 10.3109/03630269.2015.1008702
Jain D, Arjunan A, Sarathi V, Jain H, Bhandarwar A, Vuga M, Krishnamurti L (2016) Clinical events in a large prospective cohort of children with sickle cell disease in Nagpur, India: evidence against a milder clinical phenotype in India. Pediatr Blood Cancer 63(10):1814–1821
doi: 10.1002/pbc.26085
Jain D, Warthe V, Colah R, Serjeant GR (2015) Sickle cell disease in Central India: high prevalence of sickle/Beta thalassemia and severe disease phenotype. Blood 126(23):4588. https://doi.org/10.1182/blood.V126.23.4588.4588
doi: 10.1182/blood.V126.23.4588.4588
Dadheech S, Jain S, Madhulatha D, Sharma V, Joseph J, Jyothy A, Munshi A (2014) Association of Xmn1 -158 γG variant with severity and HbF levels in β-thalassemia major and sickle cell anaemia. Mol Biol Rep 41(5):3331–3337
doi: 10.1007/s11033-014-3195-5
Bhagat S, Patra PK, Thakur AS (2012) Association between XmnI polymorphism and HbF level in sickle cell disease patients from Chhattisgarh. Int J Biomed Sci 8(1):36–39
pubmed: 23675255
pmcid: 3614849
Liu D, Zhang X, Yu L, Cai R, Ma X, Zheng C, Zhou Y, Liu Q, Wei X, Lin L, Yan T, Huang J, Mohandas N, An X, Xu X (2014) KLF1 mutations are relatively more common in a thalassemia endemic region and ameliorate the severity of β-thalassemia. Blood 124(5):803–811
doi: 10.1182/blood-2014-03-561779
Hariharan P, Colah R, Ghosh K, Nadkarni A (2019) Differential role of Kruppel like factor 1 (KLF1) gene in red blood cell disorders. Genomics 111(6):1771–1776
doi: 10.1016/j.ygeno.2018.11.032
Khamphikham P, Sripichai O, Munkongdee T, Fucharoen S, Tongsima S, Smith DR (2018) Genetic variation of Krüppel-like factor 1 (KLF1) and fetal hemoglobin (HbF) levels in β0-thalassemia/HbE disease. Int J Hematol 107(3):297–310
doi: 10.1007/s12185-017-2357-3
Pereira C, Relvas L, Bento C, Abade A, Ribeiro ML, Manco L (2015) Polymorphic variations influencing fetal hemoglobin levels: association study in beta-thalassemia carriers and in normal individuals of Portuguese origin. Blood Cells Mol Dis 54(4):315–320
doi: 10.1016/j.bcmd.2015.02.001
Ngo D, Bae H, Steinberg MH, Sebastiani P, Solovieff N, Baldwin CT, Melista E, Safaya S, Farrer LA, al-Suliman AM, Albuali WH, al Bagshi MH, Naserullah Z, Akinsheye I, Gallagher P, Luo HY, Chui DHK, Farrell JJ, al-Ali AK, Alsultan A (2013) Fetal hemoglobin in sickle cell anemia: genetic studies of the Arab-Indian haplotype. Blood Cells Mol Dis 51(1):22–26
doi: 10.1016/j.bcmd.2012.12.005
Zaker-Kandjani B, Namdar-Aligoodarzi P, Azarkeivan A, Najmabadi H, Banan M (2015) Mutation screening of the Krüppel-like factor 1 gene using single-strand conformational polymorphism in a cohort of Iranian β-thalassemia patients. Hemoglobin 39(1):24–29
doi: 10.3109/03630269.2014.991023
Borgio JF, AbdulAzeez S, Al-Muslami AM, Naserullah ZA, Al-Jarrash S, Al-Suliman AM, Al-Madan MS, Al-Ali AK (2018) KLF1 gene and borderline hemoglobin A2 in Saudi population. Arch Med Sci 14(1):230–236
doi: 10.5114/aoms.2018.72245