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An Analysis of Racial and Ethnic Backgrounds Within the CASiRe International Cohort of Sickle Cell Disease Patients: Implications for Disease Phenotype and Clinical Research

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Abstract

Millions are affected by sickle cell disease (SCD) worldwide with the greatest burden in sub-Saharan Africa. While its origin lies historically within the malaria belt, ongoing changes in migration patterns have shifted the burden of disease resulting in a global public health concern. We created the Consortium for the Advancement of Sickle Cell Research (CASiRe) to understand the different phenotypes of SCD across 4 countries (USA, UK, Italy, and Ghana). Here, we report the multi-generational ethnic and racial background of 877 SCD patients recruited in Ghana (n = 365, 41.6%), the USA (n = 254, 29%), Italy (n = 81, 9.2%), and the UK (n = 177, 20.2%). West Africa (including Benin Gulf) (N = 556, 63.4%) was the most common geographic region of origin, followed by North America (N = 184, 21%), Caribbean (N = 51, 5.8%), Europe (N = 27, 3.1%), Central Africa (N = 24, 2.7%), and West Africa (excluding Benin Gulf) (N = 21, 2.4%). SCD patients in Europe were primarily West African (73%), European (10%), Caribbean (8%), and Central African (8%). In the USA, patients were largely African American (71%), Caribbean (13%), or West African (10%). Most subjects identified themselves as Black or African American; the European cohort had the largest group of Caucasian SCD patients (8%), including 21% of the Italian patients. This is the first report of a comprehensive analysis of ethnicity within an international, transcontinental group of SCD patients. The diverse ethnic backgrounds observed in our cohort raises the possibility that genetic and environmental heterogeneity within each SCD population subgroup can affect the clinical phenotype and research outcomes.

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References

  1. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331–6.

    Article  CAS  Google Scholar 

  2. Piel FB, Steinberg MH, Rees DC. Sickle cell disease. N Engl J Med. 2017;377(3):305.

    Article  Google Scholar 

  3. Inusa BPD, Colombatti R. European migration crises: the role of national hemoglobinopathy registries in improving patient access to care. Pediatr Blood Cancer. 2017;64(7). https://doi.org/10.1002/pbc.26515.

  4. Piel FB, Tatem AJ, Huang Z, Gupta S, Williams TN, Weatherall DJ. Global migration and the changing distribution of sickle haemoglobin: a quantitative study of temporal trends between 1960 and 2000. Lancet Glob Health. 2014;2(2):e80–9.

    Article  Google Scholar 

  5. Akingbola TS, Tayo BO, Salako B, Layden JE, Hsu LL, Cooper RS, et al. Comparison of patients from Nigeria and the USA highlights modifiable risk factors for sickle cell anemia complications. Hemoglobin. 2014;38(4):236–43.

    Article  CAS  Google Scholar 

  6. Saraf SL, Molokie RE, Nouraie M, Sable CA, Luchtman-Jones L, Ensing GJ, et al. Differences in the clinical and genotypic presentation of sickle cell disease around the world. Paediatr Respir Rev. 2014;15(1):4–12.

    PubMed  Google Scholar 

  7. Njamnshi AK, Wonkam A, Djientcheu VP, Ongolo-Zogo P, Obama MT, Muna WFT, et al. Stroke may appear to be rare in Saudi-Arabian and Nigerian children with sickle cell disease, but not in Cameroonian sickle cell patients. Br J Haematol. 2006;133(2):210 author reply 211.

    Article  Google Scholar 

  8. Montanaro M, Colombatti R, Pugliese M, Migliozzi C, Zani F, Guerzoni M, et al. Intellectual function evaluation of first generation immigrant children with sickle cell disease: the role of language and sociodemographic factors. Ital J Pediatr. 2013;39:36.

    Article  Google Scholar 

  9. Maitra P, Caughey M, Robinson L, Desai PC, Jones S, Nouraie M, et al. Risk factors for mortality in adult patients with sickle cell disease: a meta-analysis of studies in North America and Europe. Haematologica. 2017;102(4):626–36.

    Article  Google Scholar 

  10. Zheng Y, Maitta RW. Alloimmunisation rates of sickle cell disease patients in the United States differ from those in other geographical regions. Transfus Med. 2016;26(3):225–30.

    Article  CAS  Google Scholar 

  11. Bavarsad Shahripour R, Mortazavi MM, Barlinn K, Keikhaei B, Mousakhani H, Azarpazhooh MR, et al. Can STOP trial velocity criteria be applied to Iranian children with sickle cell disease? J Stroke. 2014;16(2):97–101.

    Article  Google Scholar 

  12. Sommet J, Alberti C, Couque N, Verlhac S, Haouari Z, Mohamed D, et al. Clinical and haematological risk factors for cerebral macrovasculopathy in a sickle cell disease newborn cohort: a prospective study. Br J Haematol. 2016;172(6):966–77.

    Article  Google Scholar 

  13. Duru KC, Noble JA, Guindo A, Yi L, Imumorin IG, Diallo DA, et al. Extensive genomic variability of knops blood group polymorphisms is associated with sickle cell disease in Africa. Evol Bioinformatics Online. 2015;11:25–33.

    CAS  Google Scholar 

  14. Noble JA, Duru KC, Guindo A, Yi L, Imumorin IG, Diallo DA, et al. Interethnic diversity of the CD209 (rs4804803) gene promoter polymorphism in African but not American sickle cell disease. PeerJ. 2015;3:e799.

    Article  Google Scholar 

  15. Kanter J, Heath LE, Knorr J, Agbenyega ET, Colombatti R, Dampier C, et al. Novel findings from the multinational DOVE study on geographic and age-related differences in pain perception and analgesic usage in children with sickle cell anaemia. Br J Haematol. 2019;184(6):1058–61.

    Article  Google Scholar 

  16. Health, N.I.O. National Institutes of Health (2001) NIH policy and guidelines on the inclusion of women and minorities as subjects in clinical research 2001; Available from: https://grants.nih.gov/policy/inclusion/women-and-minorities.htm. Accessed 28 Nov 2017.

  17. National Center on Birth Defects and Developmental Disabilities, C.f.D.C.a.P. 2019; Available from: https://www.cdc.gov/ncbddd/sicklecell/data.html. Accessed 21 Oct 2019.

  18. De Franceschi L, et al. Access to emergency departments for acute events and identification of sickle cell disease in refugees. Blood. 2019;133(19):2100–3.

    Article  Google Scholar 

  19. Inusa BPD, et al. Geographic differences in phenotype and treatment of children with sickle cell anemia from the multinational DOVE study. J Clin Med. 2019;8(11). https://doi.org/10.3390/jcm8112009.

  20. Braun L, Fausto-Sterling A, Fullwiley D, Hammonds EM, Nelson A, Quivers W, et al. Racial categories in medical practice: how useful are they? PLoS Med. 2007;4(9):e271.

    Article  Google Scholar 

  21. Moussa EY, Yassine NM, Borjac JM. New variants in beta globin gene among the Palestinian refugees with sickle cell disease in Lebanon. Saudi Med J. 2018;39(12):1253–8.

    Article  Google Scholar 

  22. Nasr A, Saleh AM, Eltoum M, Abushouk A, Hamza A, Aljada A, et al. Antibody responses to P. falciparum apical membrane antigen 1(AMA-1) in relation to haemoglobin S (HbS), HbC, G6PD and ABO blood groups among Fulani and Masaleit living in Western Sudan. Acta Trop. 2018;182:115–23.

    Article  CAS  Google Scholar 

  23. Boateng LA, Campbell AD, Davenport RD, Osei-Akoto A, Hugan S, Asamoah A, et al. Red blood cell alloimmunization and minor red blood cell antigen phenotypes in transfused Ghanaian patients with sickle cell disease. Transfusion. 2019;59(6):2016–22.

    Article  CAS  Google Scholar 

  24. Armenis I, Kalotychou V, Tzanetea R, Kollia P, Kontogeorgiou Z, Anastasopoulou D, et al. Data on eNOS T786 and G894T polymorphisms and peripheral blood eNOS mRNA levels in sickle cell disease. Data Brief. 2017;10:192–7.

    Article  Google Scholar 

  25. Afifi RA, et al. CD209-336A/G promotor polymorphism and its clinical associations in sickle cell disease Egyptian pediatric patients. Hematol Oncol Stem Cell Ther. 2018;11(2):75–81.

    Article  CAS  Google Scholar 

  26. Armenis I, Kalotychou V, Tzanetea R, Kollia P, Kontogeorgiou Z, Anastasopoulou D, et al. Prognostic value of T786C and G894T eNOS polymorphisms in sickle cell disease. Nitric Oxide. 2017;62:17–23.

    Article  CAS  Google Scholar 

  27. Afifi RAA, Sedky YM, Abd-ELKareem H, Botros SKA. IL-Ibeta+3954 C/T polymorphism and its clinical associations in Egyptian sickle cell disease patients. Int J Hematol Oncol Stem Cell Res. 2019;13(1):35–41.

    PubMed  PubMed Central  Google Scholar 

  28. Antwi-Boasiako C, et al. Association between eNOS gene polymorphism (T786C and VNTR) and sickle cell disease patients in Ghana. Diseases. 2018;6(4). https://doi.org/10.3390/diseases6040090.

  29. Pereira F, et al. A systematic literature review on the European, African and Amerindian genetic ancestry components on Brazilian health outcomes. Sci Rep. 2019;9(1):8874.

    Article  Google Scholar 

  30. Wonkam A, Makani J. Sickle cell disease in Africa: an urgent need for longitudinal cohort studies. Lancet Glob Health. 2019;7(10):e1310–e1311. https://doi.org/10.1016/S2214-109X(19)30364-X.

  31. Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376(5):429–39.

    Article  CAS  Google Scholar 

  32. Heeney MM, Hoppe CC, Abboud MR, Inusa B, Kanter J, Ogutu B, et al. A multinational trial of prasugrel for sickle cell vaso-occlusive events. N Engl J Med. 2016;374(7):625–35.

    Article  CAS  Google Scholar 

  33. Martins GLS, Paredes BD, Azevedo CM, Sampaio GLDA, Nonaka CKV, Cavalcante BRR, et al. Generation of integration-free iPS cell lines from three sickle cell disease patients from the state of Bahia, Brazil. Stem Cell Res. 2018;33:10–4.

    Article  CAS  Google Scholar 

  34. Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, el-Beshlawy A, et al. A phase 3 randomized trial of Voxelotor in sickle cell disease. N Engl J Med. 2019;381:509–19.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Thanks to Adetola Kassim, Vishwas Sakhalkar for their help in developing the questionnaire and protocol.

Funding

We would like to thank the following individuals for their contributions to this work:

Students of the University of Michigan Minority Health and Health Disparities International Research Training (MHIRT) program (Funding support: Grant # NIMHD T37MD001425), Ahmed Owda, Duna Buttner, Biana D. Oteng, Sophia Akatue, Ashya Smith, Austin Novarra, Clementine Fu, Fitz Tavernier, Lewis Graham, Rose Bamfo, Esther Kim, Haikel Halle, Rebekah Urbonya, Fatimah Farooq, Sheri Van Omen, Marianna Yamamoto.

Author information

Author notes

  1. Andrew D. Campbell and Raffaella Colombatti contributed equally to this work.

Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA

    Andrew D. Campbell, Fatimah Farooq & Rebekah Urbonya

  2. Center for Cancer and Blood Disorders, Children’s National Medical Center, Washington, DC, USA

    Andrew D. Campbell

  3. Clinic of Pediatric Hematology Oncology, Department of Women’s and Child Health, Azienda Ospedaliera-Università di Padova, Padova, Italy

    Raffaella Colombatti & Laura Sainati

  4. Division of Hematology-Oncology, New England Sickle Cell Institute, Neag Comprehensive Cancer Center, UCONN Health, University of Connecticut, Farmington, CT, USA

    Biree Andemariam

  5. ProMedica Russell J. Ebeid Children’s Hospital, Toledo, OH, USA

    Crawford Strunk

  6. Department of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Immacolata Tartaglione & Silverio Perrotta

  7. Pediatric Hematology/Oncology, Rainbow Babies and Children’s Hospital, Cleveland, OH, USA

    Connie M. Piccone

  8. Department of Pediatrics, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, Bronx, NY, USA

    Deepa Manwani

  9. Ghana Institute of Clinical Genetics, Korle Bu Teaching Hospital, Accra, Ghana

    Eugenia Vicky Asare & Fredericka Sey

  10. Department of Hematology, Korle-Bu Teaching Hospital, Accra, Ghana

    Eugenia Vicky Asare

  11. Department of Physiology, University of Ghana Medical School, Accra, Ghana

    Gifty Dankwah Boatemaa & Charles Antwi-Boasiako

  12. Division of Pediatric Hematology/Oncology, University of Illinois-Chicago, Chicago, IL, USA

    Angela Rivers

  13. Department of Child Health, Korle Bu Teaching Hospital, Accra, Ghana

    Sudha Rao & Catherine Segbefia

  14. Department of Pediatrics, Connecticut Children’s Medical Center, Hartford, CT, USA

    Donna Boruchov & William Zempsky

  15. Department of Pediatric Haematology, Evelina Children’s Hospital, Guy’s and St. Thomas NHS Trust, London, UK

    Baba Inusa

Authors
  1. Andrew D. Campbell
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Contributions

AC and RC wrote the manuscript and contributed equally to this work. BA, CS (Ghana), IT, CP, DM, EVA, DB, AR, WZ, CS (USA), BI, and CAB critically edited the manuscript. AC, RC BA, CS (USA), CP, IT, DM, DB, RU, WZ, BI, and CAB helped design the study, performed the research, and analyzed the data. EVA, DB, FF, GDB, SR, FS, and CS (Ghana) performed the research and analyzed the data. AR, FS, and LS helped design the study and analyzed the data. FS, LS, and SR reviewed the manuscript.

Corresponding author

Correspondence to Andrew D. Campbell.

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Conflict of Interest

A Campbell: research funding and consultancy from Global Blood Therapeutics (GBT), Novartis, Cyclerion; consultancy from BluebirdBio; D Manwani: research funding from Grifols; consultancy for Novartis, Pfizer, Global Blood Therapeutics; B Andemariam: consultancy for Novartis, Pfizer, NovoNordisk, Emmaus, Cyclerion, Terumo, Sanofi; DSMB: Global Blood Therapeutics; research funding: Imara; B Inusa: education funding: Novartis AstraZeneca, Global Blood Therapeutics, Celgene, Vertex; C. Strunk: consultancy Global Blood Therapeutics and Novartis; R Colombatti: research funding: Global Blood Therapeutics, Novartis. No disclosures to declare from the other co-authors.

Informed Consent and Research Involving Human Participants and/or Animals

Except at two sites (Guys and St Thomas Hospital, UK; Azienda Ospedaliera-Università di Padova, Italy) that had a previously Institutional Review Board–approved Sickle Cell Disease Registry, Institutional Review Board approval was obtained at each site and written informed consent was obtained by each patient and/or parent/guardian.

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Campbell, A.D., Colombatti, R., Andemariam, B. et al. An Analysis of Racial and Ethnic Backgrounds Within the CASiRe International Cohort of Sickle Cell Disease Patients: Implications for Disease Phenotype and Clinical Research. J. Racial and Ethnic Health Disparities 8, 99–106 (2021). https://doi.org/10.1007/s40615-020-00762-2

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