Genetic modulators of diversity in biological expression of sickle cell anemia in patients from democratic republic of Congo
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Keywords
sickle cell anemia, DR Congo, SCA haplotypes, HbF, single nucleotide polymorphisms
Abstract
Background: So far, the fetal hemoglobin (HbF) level is the most recognized modulator of sickle cell anemia (SCA) clinical expression. Variability in the HbF levels is associated with the SCA haplotypes and quantitative trait loci identified by Genome-Wide Association Studies (GWAS).
Key words: sickle cell anemia, DR Congo, SCA haplotypes, HbF, single nucleotide polymorphisms
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References
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3. Akinsheye I, Alsultan A, Solovieff N, Ngo D, Baldwin CT, Sebastiani P, Chui DH & Steinberg MH . Fetal hemoglobin in sickle cell anemia. Blood. 2011;118(1):19–27.
4. Steinberg MH, Sebastiani P. Genetic modifiers of sickle cell disease. Am J Hematol. 2012;87(8):795–803.
5. Dadheech S, Jain S, Madhulatha D, Sharma V, Joseph J, Jyothy A, Munshi A . Association of Xmn1 −158 γG variant with severity and HbF levels in β-thalassemia major and sickle cell anaemia. Mol Biol Rep. 2014;41(5):3331–37.
6. Maitra P, Caughey M, Robinson L, Desai PC, Jones S, Nouraie M, Gladwin MT, Hinderliter A, Cai J & Ataga KI. Risk factors for mortality in adult patients with sickle cell disease: a metaanalysis of studies in North America and Europe. Haematologica. 2017;102(4):626–36.
7. Steinberg MH. Fetal hemoglobin in sickle cell anemia. Blood. 2020;136(21):2392–2400.
8. Ndugwa C, Higgs D, Fisher C, Hambleton I, Mason K, Serjeant BE, Serjeant GR. Homozygous sickle cell disease in Uganda and Jamaica a comparison of Bantu and Benin haplotypes. West Indian Med J. 2012; 61(7): 684-91.
9. Al-Saqladi AW, Brabin BJ, Bin-Gadeem HA, Kanhai WA, Phylipsen M, Harteveld CL. Beta-globin gene cluster haplotypes in Yemeni children with sickle cell disease. Acta Haematol. 2010; 123(3):182-5.
10. Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. N Engl J Med.2017;376(16):1561-1573.
11. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018-2031.
12. Habara AH, Shaikho EM, Steinberg MH. Fetal hemoglobin in sickle cell anemia: The Arab-Indian haplotype and new therapeutic agents. Am J Hematol.2017; 92(11),1233-1242.
13. Gibney GT, Panhuysen CIM, So JCC, Ma ESK, Ha SY, Li CK, Lee AC, Li CK, Yuen HL, Lau YL, Johnson DM, Farrell JJ, Bisbee AB, Farrer LA, Steinberg MH, Chan LC , Chui DH. Variation and heritability of Hb F and F-cells among β-thalassemia heterozygotes in Hong Kong. Am J Hematol.2008; 83(6):458–64.
14. Lettre G, Sankaran VG, Bezerra MAC, Araújo AS, Uda M, Sanna S, Cao A, Schlessinger D, Costa FF, Hirschhorn JN, Orkin SH. DNA polymorphisms at the BCL11A , HBS1L-MYB , and β- globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proceedings of the National Academy of Sciences. 2008;105(33):11869–74.
15. Thein SL. Genetic modifiers of the β-haemoglobinopathies. Br J Haematol. 2008;141(3):357–66.
16. Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, Usala G, Busonero F, Maschio A, Albai G, Piras MG, Sestu N, Lai S, Dei M, Mulas A, Crisponi L, Naitza S, Asunis I, Deiana M, Nagaraja R, Perseu L, Satta S, Cipollina MD, Sollaino C, Moi P, Hirschhorn JN, Orkin SH, Abecasis GR, Schlessinger D, Cao A. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of β-thalassemia. Proceedings of the National Academy of Sciences. 2008;105(5):1620–25.
17. Nuinoon M, Makarasara W, Mushiroda T, Setianingsih I, Wahidiyat PA, Sripichai O, Kumasaka N, Takahashi A, Svasti S, Munkongdee T, Mahasirimongkol S, Peerapittayamongkol C, Viprakasit V, Kamatani N, Winichagoon P, Kubo M, Nakamura Y , Fucharoen S. A genome-wide association identified the common genetic variants influence disease severity in β0- thalassemia/hemoglobin E. Hum Genet. 2010;127(3):303–14.
18. Solovieff N, Milton JN, Hartley SW, Sherva R, Sebastiani P, Dworkis DA, Klings ES, Farrer LA, Garrett ME, Ashley-Koch A, Telen MJ, Fucharoen S, Ha SY, Li CK, Chui DH, Baldwin CT , Steinberg MH. Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5′ olfactory receptor gene cluster. Blood. 2010;115(9):1815–22.
19. Thein SL, Menzel S, Lathrop M, Garner C . Control of fetal hemoglobin: new insights emerging from genomics and clinical implications. Hum Mol Genet.2009; 18(R2):R216-23.
20. Galarneau G, Palmer CD, Sankaran VG, Orkin SH, Hirschhorn JN, Lettre G. Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation. Nat Genet.2010;42(12):1049-51.
21. Gravia A, Chondrou V, Kolliopoulou A, Kourakli A , John A, Symeonidis A, Ali BR, Sgourou A, Papachatzopoulou A, Katsila T , Patrinos GP. Correlation of SIN3A genomic variants with β-hemoglobinopathies disease severity and hydroxyurea treatment efficacy. Pharmacogenomics. 2016;17(16):1785–93.
22. Bhatnagar P, Purvis S, Barron-Casella E, G DeBaun MR, Casella JF, Arking DE , Keefer JR . Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients. J Hum Genet. 2011;56(4):316–23.
23. Tshilolo L, Aissi LM, Lukusa D, Kinsiama C, Wembonyama S, Gulbis B, Vertongen F. Neonatal screening for sickle cell anaemia in the Democratic Republic of the Congo: experience from a pioneer project on 31 204 newborns. J Clin Pathol.2009; 62(1) : 35-8.
24. Mikobi TM, Tshilobo Lukusa P, Aloni M Lumaka AZ, Kaba DK, Devriendt K, Matthijs G, Mbuyi Muamba JM, Race V. Protective BCL11A and HBS1L-MYB polymorphisms in a cohort of 102 Congolese patients suffering from sickle cell anemia. J Clin Lab Anal. 2018;32(1):e22207.
25. Ngole M, Race V, Mbayabo G, Lumbala P, Songo C, Lukusa PT, Devriendt K, Matthijs G, Lumaka A . DNA testing for sickle cell anemia in Africa: Implementation choices for the Democratic Republic of Congo. J Clin Lab Anal. 2022;36(5):e24398.
26. Wonkam A, Ngo Bitoungui VJ, Vorster AA, Vorster AA, Ramesar R, Cooper RS, Tayo B, Lettre G, Ngogang J. Association of Variants at BCL11A and HBS1L-MYB with Hemoglobin F and Hospitalization Rates among Sickle Cell Patients in Cameroon. PLoS One. 2014;9(3):e92506.
27. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res.1988;16(3) :1215.
28. Shaikho EM, Farrell JJ, Alsultan A, Qutub H, Al-Ali AK, Figueiredo MS, Chui DHK, Farrer LA, Murphy GJ, Mostoslavsky G, Sebastiani P, Steinberg MH . A phased SNP-based classification of sickle cell anemia HBB haplotypes. BMC Genomics.2017;18(1):608.
29. Okumura JV, Silva DGH, Torres LS, Belini-Junior E, Venancio LPR., Carrocini GCS, Nascimento PP, Lobo CLC , Bonini-Domingos CR. Atypical β-S haplotypes: classification and genetic modulation in patients with sickle cell anemia. J Hum Genet.2019;64(3):239- 248.
30. Cantsilieris S, Stessman HA, Shendure J, Eichler EE. Targeted Capture and High Throughput Sequencing Using Molecular Inversion Probes (MIPs). Methods Mol Bio.2017;1492:95- 106.
31. Magoč T, Salzberg SL. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics.2011;27(21):2957-63.
32. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(14), 1754-176.
33. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA . The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res.2010;20(9),1297-303.
34. Borges E, Tchonhi C, Couto CSB, Gomes V, Amorim A, Prata MJ, Brito M. . Unusual β-Globin Haplotype Distribution in Newborns from Bengo, Angola. Hemoglobin.2019; 43(3):149-154.
35. Delgadinho M, Ginete C, Santos B, Miranda A, Brito M. Genotypic Diversity among Angolan Children with Sickle Cell Anemia. Int J Environ Res Public Health.2021; 18(10):5417.
36. Mouélé R, Pambou O, Feingold J, Galactéros F. Alpha-thalassemia in Bantu population from Congo-Brazzaville: its interaction with sickle cell anemia. Hum Hered. 2000;50(2):118- 25.
37. Tshilolo L, Tomlinson G, Williams TN, Santos B, Olupot-Olupot P, Lane A, Aygun B, Stuber SE, Latham TS, McGann PT, Ware RE; REACH Investigators. Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med.2019;380(2) :121-131.
38. Flahaux ML, Schoumaker B. Democratic Republic of the Congo: A Migration History Marked by Crises and Restrictions. The online Journal of Migration Policy Institute;2016: April 20. www.migrationpolicy.org . Accessed March 15, 2022.
39. Bitoungui VJ, Pule GD, Hanchard N, Ngogang J, Wonkam A. Beta-globin gene haplotypes among cameroonians and review of the global distribution: is there a case for a single sickle mutation origin in Africa? OMICS.2015;19(3):171-9.
40. Makani J, Menzel S, Nkya S, et al. Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia. Blood.2011; 117(4):1390–92.
41. Adeyemo TA, Ojewunmi OO, Oyetunji IA, Rooks H, Rees DC, Akinsulie AO, Akanmu AS, Thein SL, Menzel S. A survey of genetic fetal-haemoglobin modifiers in Nigerian patients with sickle cell anaemia. PLoS One.2018; 13(6):e0197927.
42. Mtatiro SN, Singh T, Rooks H, Mgaya J, Mariki H, Soka D, Mmbando B, Msaki E, Kolder I, Thein SL, Menzel S, Cox SE, Makani J, Barrett JC. Genome Wide Association Study of Fetal Hemoglobin in Sickle Cell Anemia in Tanzania. PLoS One.2014; 9(11):e111464.
43. Pule GD, Ngo Bitoungui VJ, Chetcha Chemegni B, Kengne AP, Antonarakis S, Wonkam A. Association between Variants at BCL11A Erythroid-Specific Enhancer and Fetal Hemoglobin Levels among Sickle Cell Disease Patients in Cameroon: Implications for Future Therapeutic Interventions. OMICS.2015; 19(10):627–31.
44. Chaouch L, Moumni I, Ouragini H, Darragi I, Kalai M, Chaouachi D, Boudrigua I, Hafsia R, Abbes S. rs11886868 and rs4671393 of BCL11A associated with HbF level variation and modulate clinical events among sickle cell anemia patients, Hematology.2016; 21:7:425-429.
45. Creary LE, Ulug P, Menzel S, . McKenzie CA, Hanchard NA, Taylor V, Farrall M, Forrester TE, Thein SL. Genetic Variation on Chromosome 6 Influences F Cell Levels in Healthy Individuals of African Descent and HbF Levels in Sickle Cell Patients. PLoS One. 2009;4(1):e4218.
46. Thein SL, Menzel S, Peng X, Best S, Jiang J, Close J, Silver N, Gerovasilli A, Ping C, Yamaguchi M, Wahlberg K, Ulug P, Spector TD, Garner C, Matsuda F, Farrall M, Lathrop M. Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults. Proceedings of the National Academy of Sciences.2007;104(27):11346–51.
47. Gilman J, Huisman T. Two independent genetic factors in the beta-globin gene cluster are associated with high G gamma-levels in the HbF of SS patients. Blood. 1984;64(2):452–57.
48. Al‐Allawi N, Qadir SMA, Puehringer H, Chui DHK, Farrell JJ , Oberkanins C. The association of HBG2 , BCL11A, and HMIP polymorphisms with fetal hemoglobin and clinical phenotype in Iraqi Kurds with sickle cell disease. Int J Lab Hematol.2019;41(1):87–93.
49. Bhanushali AA, Patra PK, Pradhan S, Khanka SS, Singh S , Das BR. Genetics of fetal hemoglobin in tribal Indian patients with sickle cell anemia. Translational Research.2015; 165(6):696– 703.
2. Aghajani F, Mahdavi MR, Kosaryan M, Mahdavi M, Hamidi M, Jalali H. Identification of β-globin haplotypes linked to sickle hemoglobin (HbS) alleles in Mazandaran province, Iran. Genes Genet Syst.2017; 91(6):311-313.
3. Akinsheye I, Alsultan A, Solovieff N, Ngo D, Baldwin CT, Sebastiani P, Chui DH & Steinberg MH . Fetal hemoglobin in sickle cell anemia. Blood. 2011;118(1):19–27.
4. Steinberg MH, Sebastiani P. Genetic modifiers of sickle cell disease. Am J Hematol. 2012;87(8):795–803.
5. Dadheech S, Jain S, Madhulatha D, Sharma V, Joseph J, Jyothy A, Munshi A . Association of Xmn1 −158 γG variant with severity and HbF levels in β-thalassemia major and sickle cell anaemia. Mol Biol Rep. 2014;41(5):3331–37.
6. Maitra P, Caughey M, Robinson L, Desai PC, Jones S, Nouraie M, Gladwin MT, Hinderliter A, Cai J & Ataga KI. Risk factors for mortality in adult patients with sickle cell disease: a metaanalysis of studies in North America and Europe. Haematologica. 2017;102(4):626–36.
7. Steinberg MH. Fetal hemoglobin in sickle cell anemia. Blood. 2020;136(21):2392–2400.
8. Ndugwa C, Higgs D, Fisher C, Hambleton I, Mason K, Serjeant BE, Serjeant GR. Homozygous sickle cell disease in Uganda and Jamaica a comparison of Bantu and Benin haplotypes. West Indian Med J. 2012; 61(7): 684-91.
9. Al-Saqladi AW, Brabin BJ, Bin-Gadeem HA, Kanhai WA, Phylipsen M, Harteveld CL. Beta-globin gene cluster haplotypes in Yemeni children with sickle cell disease. Acta Haematol. 2010; 123(3):182-5.
10. Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. N Engl J Med.2017;376(16):1561-1573.
11. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018-2031.
12. Habara AH, Shaikho EM, Steinberg MH. Fetal hemoglobin in sickle cell anemia: The Arab-Indian haplotype and new therapeutic agents. Am J Hematol.2017; 92(11),1233-1242.
13. Gibney GT, Panhuysen CIM, So JCC, Ma ESK, Ha SY, Li CK, Lee AC, Li CK, Yuen HL, Lau YL, Johnson DM, Farrell JJ, Bisbee AB, Farrer LA, Steinberg MH, Chan LC , Chui DH. Variation and heritability of Hb F and F-cells among β-thalassemia heterozygotes in Hong Kong. Am J Hematol.2008; 83(6):458–64.
14. Lettre G, Sankaran VG, Bezerra MAC, Araújo AS, Uda M, Sanna S, Cao A, Schlessinger D, Costa FF, Hirschhorn JN, Orkin SH. DNA polymorphisms at the BCL11A , HBS1L-MYB , and β- globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proceedings of the National Academy of Sciences. 2008;105(33):11869–74.
15. Thein SL. Genetic modifiers of the β-haemoglobinopathies. Br J Haematol. 2008;141(3):357–66.
16. Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, Usala G, Busonero F, Maschio A, Albai G, Piras MG, Sestu N, Lai S, Dei M, Mulas A, Crisponi L, Naitza S, Asunis I, Deiana M, Nagaraja R, Perseu L, Satta S, Cipollina MD, Sollaino C, Moi P, Hirschhorn JN, Orkin SH, Abecasis GR, Schlessinger D, Cao A. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of β-thalassemia. Proceedings of the National Academy of Sciences. 2008;105(5):1620–25.
17. Nuinoon M, Makarasara W, Mushiroda T, Setianingsih I, Wahidiyat PA, Sripichai O, Kumasaka N, Takahashi A, Svasti S, Munkongdee T, Mahasirimongkol S, Peerapittayamongkol C, Viprakasit V, Kamatani N, Winichagoon P, Kubo M, Nakamura Y , Fucharoen S. A genome-wide association identified the common genetic variants influence disease severity in β0- thalassemia/hemoglobin E. Hum Genet. 2010;127(3):303–14.
18. Solovieff N, Milton JN, Hartley SW, Sherva R, Sebastiani P, Dworkis DA, Klings ES, Farrer LA, Garrett ME, Ashley-Koch A, Telen MJ, Fucharoen S, Ha SY, Li CK, Chui DH, Baldwin CT , Steinberg MH. Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5′ olfactory receptor gene cluster. Blood. 2010;115(9):1815–22.
19. Thein SL, Menzel S, Lathrop M, Garner C . Control of fetal hemoglobin: new insights emerging from genomics and clinical implications. Hum Mol Genet.2009; 18(R2):R216-23.
20. Galarneau G, Palmer CD, Sankaran VG, Orkin SH, Hirschhorn JN, Lettre G. Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation. Nat Genet.2010;42(12):1049-51.
21. Gravia A, Chondrou V, Kolliopoulou A, Kourakli A , John A, Symeonidis A, Ali BR, Sgourou A, Papachatzopoulou A, Katsila T , Patrinos GP. Correlation of SIN3A genomic variants with β-hemoglobinopathies disease severity and hydroxyurea treatment efficacy. Pharmacogenomics. 2016;17(16):1785–93.
22. Bhatnagar P, Purvis S, Barron-Casella E, G DeBaun MR, Casella JF, Arking DE , Keefer JR . Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients. J Hum Genet. 2011;56(4):316–23.
23. Tshilolo L, Aissi LM, Lukusa D, Kinsiama C, Wembonyama S, Gulbis B, Vertongen F. Neonatal screening for sickle cell anaemia in the Democratic Republic of the Congo: experience from a pioneer project on 31 204 newborns. J Clin Pathol.2009; 62(1) : 35-8.
24. Mikobi TM, Tshilobo Lukusa P, Aloni M Lumaka AZ, Kaba DK, Devriendt K, Matthijs G, Mbuyi Muamba JM, Race V. Protective BCL11A and HBS1L-MYB polymorphisms in a cohort of 102 Congolese patients suffering from sickle cell anemia. J Clin Lab Anal. 2018;32(1):e22207.
25. Ngole M, Race V, Mbayabo G, Lumbala P, Songo C, Lukusa PT, Devriendt K, Matthijs G, Lumaka A . DNA testing for sickle cell anemia in Africa: Implementation choices for the Democratic Republic of Congo. J Clin Lab Anal. 2022;36(5):e24398.
26. Wonkam A, Ngo Bitoungui VJ, Vorster AA, Vorster AA, Ramesar R, Cooper RS, Tayo B, Lettre G, Ngogang J. Association of Variants at BCL11A and HBS1L-MYB with Hemoglobin F and Hospitalization Rates among Sickle Cell Patients in Cameroon. PLoS One. 2014;9(3):e92506.
27. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res.1988;16(3) :1215.
28. Shaikho EM, Farrell JJ, Alsultan A, Qutub H, Al-Ali AK, Figueiredo MS, Chui DHK, Farrer LA, Murphy GJ, Mostoslavsky G, Sebastiani P, Steinberg MH . A phased SNP-based classification of sickle cell anemia HBB haplotypes. BMC Genomics.2017;18(1):608.
29. Okumura JV, Silva DGH, Torres LS, Belini-Junior E, Venancio LPR., Carrocini GCS, Nascimento PP, Lobo CLC , Bonini-Domingos CR. Atypical β-S haplotypes: classification and genetic modulation in patients with sickle cell anemia. J Hum Genet.2019;64(3):239- 248.
30. Cantsilieris S, Stessman HA, Shendure J, Eichler EE. Targeted Capture and High Throughput Sequencing Using Molecular Inversion Probes (MIPs). Methods Mol Bio.2017;1492:95- 106.
31. Magoč T, Salzberg SL. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics.2011;27(21):2957-63.
32. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(14), 1754-176.
33. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA . The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res.2010;20(9),1297-303.
34. Borges E, Tchonhi C, Couto CSB, Gomes V, Amorim A, Prata MJ, Brito M. . Unusual β-Globin Haplotype Distribution in Newborns from Bengo, Angola. Hemoglobin.2019; 43(3):149-154.
35. Delgadinho M, Ginete C, Santos B, Miranda A, Brito M. Genotypic Diversity among Angolan Children with Sickle Cell Anemia. Int J Environ Res Public Health.2021; 18(10):5417.
36. Mouélé R, Pambou O, Feingold J, Galactéros F. Alpha-thalassemia in Bantu population from Congo-Brazzaville: its interaction with sickle cell anemia. Hum Hered. 2000;50(2):118- 25.
37. Tshilolo L, Tomlinson G, Williams TN, Santos B, Olupot-Olupot P, Lane A, Aygun B, Stuber SE, Latham TS, McGann PT, Ware RE; REACH Investigators. Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med.2019;380(2) :121-131.
38. Flahaux ML, Schoumaker B. Democratic Republic of the Congo: A Migration History Marked by Crises and Restrictions. The online Journal of Migration Policy Institute;2016: April 20. www.migrationpolicy.org . Accessed March 15, 2022.
39. Bitoungui VJ, Pule GD, Hanchard N, Ngogang J, Wonkam A. Beta-globin gene haplotypes among cameroonians and review of the global distribution: is there a case for a single sickle mutation origin in Africa? OMICS.2015;19(3):171-9.
40. Makani J, Menzel S, Nkya S, et al. Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia. Blood.2011; 117(4):1390–92.
41. Adeyemo TA, Ojewunmi OO, Oyetunji IA, Rooks H, Rees DC, Akinsulie AO, Akanmu AS, Thein SL, Menzel S. A survey of genetic fetal-haemoglobin modifiers in Nigerian patients with sickle cell anaemia. PLoS One.2018; 13(6):e0197927.
42. Mtatiro SN, Singh T, Rooks H, Mgaya J, Mariki H, Soka D, Mmbando B, Msaki E, Kolder I, Thein SL, Menzel S, Cox SE, Makani J, Barrett JC. Genome Wide Association Study of Fetal Hemoglobin in Sickle Cell Anemia in Tanzania. PLoS One.2014; 9(11):e111464.
43. Pule GD, Ngo Bitoungui VJ, Chetcha Chemegni B, Kengne AP, Antonarakis S, Wonkam A. Association between Variants at BCL11A Erythroid-Specific Enhancer and Fetal Hemoglobin Levels among Sickle Cell Disease Patients in Cameroon: Implications for Future Therapeutic Interventions. OMICS.2015; 19(10):627–31.
44. Chaouch L, Moumni I, Ouragini H, Darragi I, Kalai M, Chaouachi D, Boudrigua I, Hafsia R, Abbes S. rs11886868 and rs4671393 of BCL11A associated with HbF level variation and modulate clinical events among sickle cell anemia patients, Hematology.2016; 21:7:425-429.
45. Creary LE, Ulug P, Menzel S, . McKenzie CA, Hanchard NA, Taylor V, Farrall M, Forrester TE, Thein SL. Genetic Variation on Chromosome 6 Influences F Cell Levels in Healthy Individuals of African Descent and HbF Levels in Sickle Cell Patients. PLoS One. 2009;4(1):e4218.
46. Thein SL, Menzel S, Peng X, Best S, Jiang J, Close J, Silver N, Gerovasilli A, Ping C, Yamaguchi M, Wahlberg K, Ulug P, Spector TD, Garner C, Matsuda F, Farrall M, Lathrop M. Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults. Proceedings of the National Academy of Sciences.2007;104(27):11346–51.
47. Gilman J, Huisman T. Two independent genetic factors in the beta-globin gene cluster are associated with high G gamma-levels in the HbF of SS patients. Blood. 1984;64(2):452–57.
48. Al‐Allawi N, Qadir SMA, Puehringer H, Chui DHK, Farrell JJ , Oberkanins C. The association of HBG2 , BCL11A, and HMIP polymorphisms with fetal hemoglobin and clinical phenotype in Iraqi Kurds with sickle cell disease. Int J Lab Hematol.2019;41(1):87–93.
49. Bhanushali AA, Patra PK, Pradhan S, Khanka SS, Singh S , Das BR. Genetics of fetal hemoglobin in tribal Indian patients with sickle cell anemia. Translational Research.2015; 165(6):696– 703.
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Dec 31, 2024
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NGOLE, M. (2024) “Genetic modulators of diversity in biological expression of sickle cell anemia in patients from democratic republic of Congo”, Mediterranean Journal of Hematology and Infectious Diseases, 17(1), p. e2025001. doi: 10.4084/MJHID.2025.001.
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Author Biography
MAMY NGOLE, Center for Human Genetics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo_Department of Medical Biology, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo_ Center for Human Genetics, Faculty of Medicine, KU Leuven, Leuven, Belgium
Center for Human Genetics, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo (Laboratory supervisor)
Department of Medical Biology, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo (Laboratory supervisor)
Center for Human Genetics, Faculty of Medicine, KU Leuven, Leuven, Belgium (PhD student)