The relationship between the variations in GÎ³ and AÎ³ promotors and the Hereditary Persistence of Fetal Hemoglobin (HPFH)

Muhsin Aydin; Eyyup Rencuzogullari; Ayse Dalyan; Suleyman Bayram; Ahmet Genc

doi:10.14715/cmb/2018.64.1.7

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Vol. 64 No. 1: Issue 1

Issue Published : February 7, 2018

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The relationship between the variations in GÎ³ and AÎ³ promotors and the Hereditary Persistence of Fetal Hemoglobin (HPFH)

https://doi.org/10.14715/cmb/2018.64.1.7

Muhsin Aydin

Departmant of Biology, Faculty of Science and Letters, Adiyaman University, Adiyaman, Turkey

Eyyup Rencuzogullari

Departmant of Biology, Faculty of Science and Letters, Adiyaman University, Adiyaman, Turkey

Ayse Dalyan

Departmant of Biology, Natural and Applied Sciences Institute, Adiyaman University, Adiyaman, Turkey

Suleyman Bayram

Department of Nursing, School of Health, Adiyaman University, Adiyaman, Turkey

Ahmet Genc

Vocational School of Health Services, Adiyaman Univesity, Adiyaman, Turkey

Corresponding Author(s) : Muhsin Aydin

muhsin.aydin@live.com

Cellular and Molecular Biology, Vol. 64 No. 1: Issue 1
Article Published : January 31, 2018

Abstract

In the present study, sixty-two samples that have 1.5% and upper level of fetal hemoglobin (HbF), were examined to investigate the relationship between HbF level and non-deletional mutations in both GÎ³ (G gamma) globin (HBG2) and AÎ³ (A gamma) globin (HBG1) genes. Four variations were observed in the promotor of GÎ³ gene, which are -158C/T, -309A/G, -369C/G, and -567T/G. Also, four variations were observed in the 5'-UTR (untranslated regions) and promotor of AÎ³ gene, which are +25G/A, -369G/C, -499T/A, and -588G/A. One -222/-225 AGCA del homozygous and six variations as heterozygous in A gamma globin gene promotor region were also observed. The results of the current study suggested that there was a significant relationship between high HbF levels and two variations (-309A/T and -369C/G) in GÎ³ gene promotor. Additionally, a significant relationship between two variations (+25G/A and -499T/A) in AÎ³ gene promotor was also observed. Furthermore, the persons who carry these variations with high levels of HbF indicated that there might be a haplotype effect between these variations.

Keywords

Hemoglobin A gamma G gamma Hereditary fetal hemoglobin GÎ³ and AÎ³ promotors.

Aydin, M., Rencuzogullari, E., Dalyan, A., Bayram, S., & Genc, A. (2018). The relationship between the variations in GÎ³ and AÎ³ promotors and the Hereditary Persistence of Fetal Hemoglobin (HPFH). Cellular and Molecular Biology, 64(1), 32–39. https://doi.org/10.14715/cmb/2018.64.1.7

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References

Thompson M, Mcinnes RR, Willard HF. Genetics in Medicine, 5th edn. B. Saunders Comp. Philadelphia, USA, 1991.
Lukens JN. The abnormal hemoglobins: General principles. In: Wintrobe's Clinical Hematology (eds. G.R. Lee, J. Foerster, J. Lukons, F. Poraskev, J.P. Greer & G.M. Rodgers), 10th edn. Williams and Wilkins, A Waverly Company, Baltimore, USA, 1999, pp. 1329-43.
Klug WS, Cummings MR, Spencer CA. Genetik Kavramlar (Translation ed. í–NER, C.), 8th edn. Palme Yayınları, Ankara, TR, 2011, pp. 485-515. (In Turkish).
Forget BG. Molecular basis of hereditary persistence of fetal hemoglobin. Ann NY Acad Sci 1998; 850:38–44.
Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull. World Health Organ 2001; 79:704-12.
Genç A. Hemoglobin Varyantlarının DNA Dizi Analizi ile Belirlenmesi. í‡ukurova íœniversitesi, Sağlık Bilimleri Enstitüsü, Adana, Master's Thesis, 2005, pp. 108. (In Turkish).
Bahadir A, Köseler A, Atalay A, Koyuncu H, Akar E, Akar N et al. HbD-Los A2geles [beta121(GH4)Glu>Gln] and HbBeograd [beta121(GH4)Glu>Val]: implications for their laboratory iıagnosis and genetic origins. Turk J Hematol 2009; 26:17-20.
Fucharoen S, Pengjam Y, Surapot S, Fucharoen G, Sanchaisuriya K. Molecular and hematological characterization of HPFH-6/Indian deletion-inversion G gamma (A gammadeltabeta)0-thalassemia and Ggamma(Agammadeltabeta)0-thalassemia/HbE in Thai patients. Am J Hematol 2002; 71:109-13.
Huisman THJ. Gamma chain abnormal human fetal hemoglobins variants. Am J Hematol 1997; 55:159-63.
Manca L, Masala B. Disorders of the synthesis of human fetal hemoglobin. IUBMB Life 2008; 60:94-111.
Nagel RL. Disorder of Hemoglobin Function and Stability. In: Blood: Principles and Practice of Hematology (eds. R.I. Handin, S.E. Lux, & T.P. Stossel), Lippincott Williams&Wilkins, Philadelpphia, USA, 2003, pp. 1597-654.
Van Der Padt A, Bouva MJ, Auwerda JJ, Dees A, Harteveld CL, Giordano PC. Adult onset of a thalassemia intermedia genotype in association with a -alpha-3.7 homozygosity. Hb G-Accra [beta73(e17)Asp-->Asn] in combination with beta- and alpha-thalassemia in the same family. Hemoglobin 2005; 29:269-76.
Bouva MJ, Harteveld CL, Bakker-Verweij G, van Delft P, Giordano PC. GÎ³ -37 (A-T): A new nondeletional hereditary persistence of fetal hemoglobin determinant associated with the rare codon 91 (+t) d0-thalassemia. Hemoglobin 2006; 30:371–7.
Schroeder WA, Huisman THJ, Shelton JR, Shelton JB, Kleihauer EF, Dozy AM et al. Evidence for multiple structural genes for the gamma chain of human fetal hemoglobin. Proc Natl Acad Sci USA 1968; 60:537-44.
Stoming TA, Stoming GS, Lanclos KD, Fei YJ, Altay C, Kutlar F et al. An AÎ³ type of nondeletional hereditary persistence of fetal hemoglobin with a Tâ†’C mutation at position –175 to the cap site of the AÎ³ globin gene. Blood 1989; 73:329-33.
Rochette J, Craig JE, Thein SL. Fetal hemoglobin levels in adults. Blood Rev 1994; 8:213-24.
Langdon SD, Kaufman RE. Gamma-globin gene promoter elements required for interaction with globin enhancers. Blood 1998; 91:309-18.
Cui J, Baysdorfer C, Azimi M, Vichinsky EP, Hoppe CC. Identification of three novel HbF variants: HbF-Hayward [GÎ³1(NA1)Glyâ†’Asp, GGT>GAT], Hb F-Chori-I[AÎ³T16(A13)Glyâ†’Asp,GGC>GAC] and Hb F-Chori-II [AÎ³I29(B11)Glyâ†’Glu, GGA>GAA]. Hemoglobin 2012; 36:305-09.
Motum PI, Lindeman R, Harvey MP, Trent RJ. Comparative studies of nondeletional HPFH gamma-globin gene promoters. Exp Hematol 1993; 21:852-58.
Tasiopoulou M, Boussiou M, Sinopoulou K, Moraitis G, Loutradi-Anagnostou A et al. GÎ³-196 Câ†’T, AÎ³-201 Câ†’T: Two novel mutations in the promoter region of the Î³-globin genes associated with nondeletional hereditary persistence of fetal hemoglobin in Greece. Blood Cells Mol Dis 40:320-32.
Coleman MB, Adams JG, Steinberg MH, Plonczynski MW, Harrel AH, Castro O et al. GyAy( Î²+) hereditary persistence of fetal hemoglobin: The Gy -158 Câ†’T mutation in cis to the -175 Tâ†’C mutation of the Ay-globin gene results in increased Gy-globin synthesis. Am J Hematol 1993; 42:186-90.
Pereira C, Relvas L, Bento C, Abade A, Ribeiro ML, Manco L. Polymorphic variations influencing fetal hemoglobin levels: Association study in beta-thalassemia carriers and in normal individuals of Portuguese origin. Blood Cells Mol Dis 2015; 54:315–20.

References

Thompson M, Mcinnes RR, Willard HF. Genetics in Medicine, 5th edn. B. Saunders Comp. Philadelphia, USA, 1991.

Lukens JN. The abnormal hemoglobins: General principles. In: Wintrobe's Clinical Hematology (eds. G.R. Lee, J. Foerster, J. Lukons, F. Poraskev, J.P. Greer & G.M. Rodgers), 10th edn. Williams and Wilkins, A Waverly Company, Baltimore, USA, 1999, pp. 1329-43.

Klug WS, Cummings MR, Spencer CA. Genetik Kavramlar (Translation ed. í–NER, C.), 8th edn. Palme Yayınları, Ankara, TR, 2011, pp. 485-515. (In Turkish).

Forget BG. Molecular basis of hereditary persistence of fetal hemoglobin. Ann NY Acad Sci 1998; 850:38–44.

Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull. World Health Organ 2001; 79:704-12.

Genç A. Hemoglobin Varyantlarının DNA Dizi Analizi ile Belirlenmesi. í‡ukurova íœniversitesi, Sağlık Bilimleri Enstitüsü, Adana, Master's Thesis, 2005, pp. 108. (In Turkish).

Bahadir A, Köseler A, Atalay A, Koyuncu H, Akar E, Akar N et al. HbD-Los A2geles [beta121(GH4)Glu>Gln] and HbBeograd [beta121(GH4)Glu>Val]: implications for their laboratory iıagnosis and genetic origins. Turk J Hematol 2009; 26:17-20.

Fucharoen S, Pengjam Y, Surapot S, Fucharoen G, Sanchaisuriya K. Molecular and hematological characterization of HPFH-6/Indian deletion-inversion G gamma (A gammadeltabeta)0-thalassemia and Ggamma(Agammadeltabeta)0-thalassemia/HbE in Thai patients. Am J Hematol 2002; 71:109-13.

Huisman THJ. Gamma chain abnormal human fetal hemoglobins variants. Am J Hematol 1997; 55:159-63.

Manca L, Masala B. Disorders of the synthesis of human fetal hemoglobin. IUBMB Life 2008; 60:94-111.

Nagel RL. Disorder of Hemoglobin Function and Stability. In: Blood: Principles and Practice of Hematology (eds. R.I. Handin, S.E. Lux, & T.P. Stossel), Lippincott Williams&Wilkins, Philadelpphia, USA, 2003, pp. 1597-654.

Van Der Padt A, Bouva MJ, Auwerda JJ, Dees A, Harteveld CL, Giordano PC. Adult onset of a thalassemia intermedia genotype in association with a -alpha-3.7 homozygosity. Hb G-Accra [beta73(e17)Asp-->Asn] in combination with beta- and alpha-thalassemia in the same family. Hemoglobin 2005; 29:269-76.

Bouva MJ, Harteveld CL, Bakker-Verweij G, van Delft P, Giordano PC. GÎ³ -37 (A-T): A new nondeletional hereditary persistence of fetal hemoglobin determinant associated with the rare codon 91 (+t) d0-thalassemia. Hemoglobin 2006; 30:371–7.

Schroeder WA, Huisman THJ, Shelton JR, Shelton JB, Kleihauer EF, Dozy AM et al. Evidence for multiple structural genes for the gamma chain of human fetal hemoglobin. Proc Natl Acad Sci USA 1968; 60:537-44.

Stoming TA, Stoming GS, Lanclos KD, Fei YJ, Altay C, Kutlar F et al. An AÎ³ type of nondeletional hereditary persistence of fetal hemoglobin with a Tâ†’C mutation at position –175 to the cap site of the AÎ³ globin gene. Blood 1989; 73:329-33.

Rochette J, Craig JE, Thein SL. Fetal hemoglobin levels in adults. Blood Rev 1994; 8:213-24.

Langdon SD, Kaufman RE. Gamma-globin gene promoter elements required for interaction with globin enhancers. Blood 1998; 91:309-18.

Cui J, Baysdorfer C, Azimi M, Vichinsky EP, Hoppe CC. Identification of three novel HbF variants: HbF-Hayward [GÎ³1(NA1)Glyâ†’Asp, GGT>GAT], Hb F-Chori-I[AÎ³T16(A13)Glyâ†’Asp,GGC>GAC] and Hb F-Chori-II [AÎ³I29(B11)Glyâ†’Glu, GGA>GAA]. Hemoglobin 2012; 36:305-09.

Motum PI, Lindeman R, Harvey MP, Trent RJ. Comparative studies of nondeletional HPFH gamma-globin gene promoters. Exp Hematol 1993; 21:852-58.

Tasiopoulou M, Boussiou M, Sinopoulou K, Moraitis G, Loutradi-Anagnostou A et al. GÎ³-196 Câ†’T, AÎ³-201 Câ†’T: Two novel mutations in the promoter region of the Î³-globin genes associated with nondeletional hereditary persistence of fetal hemoglobin in Greece. Blood Cells Mol Dis 40:320-32.

Coleman MB, Adams JG, Steinberg MH, Plonczynski MW, Harrel AH, Castro O et al. GyAy( Î²+) hereditary persistence of fetal hemoglobin: The Gy -158 Câ†’T mutation in cis to the -175 Tâ†’C mutation of the Ay-globin gene results in increased Gy-globin synthesis. Am J Hematol 1993; 42:186-90.

Pereira C, Relvas L, Bento C, Abade A, Ribeiro ML, Manco L. Polymorphic variations influencing fetal hemoglobin levels: Association study in beta-thalassemia carriers and in normal individuals of Portuguese origin. Blood Cells Mol Dis 2015; 54:315–20.

Author biographies is not available.