Sickle cell disease in the post genomic era: A monogenic disease with a polygenic phenotype

Genomics Insights

Volumn 2, Issue 1, 2009, Pages 23-48

  Driss, A ^a   Asare, K O ^a   Hibbert, J M ^a   Gee, B E ^a   Adamkiewicz, T V ^a   Stiles, J K ^a  

^a MOREHOUSE SCHOOL OF MEDICINE   (United States)

Author keywords

Drepanocytose; Genomics; Hbs; Hemoglobin; Hemoglobinopathies; Rbc

Indexed keywords

EID: 77956373700     PISSN: None     EISSN: 11786310     Source Type: Journal    
DOI: 10.4137/gei.s2626     Document Type: Review

References (148)

1. Angastiniotis M, Modell B. Global epidemiology of hemoglobin disorders. Ann NY Acad Sci. 1998 Jun 30;850:251-69.
2. Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ. 2001;79(8):704-12.
3. Steinberg MH. Predicting clinical severity in sickle cell anaemia. Br J Haematol. 2005 May;129(4):465-81.
4. Kutlar A. Sickle cell disease: a multigenic perspective of a single gene disorder. Hemoglobin. 2007;31(2):209-24.
5. Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. Jama. 2005 Apr 6;293(13):1653-62.
6. Steinberg MH. Modulation of fetal hemoglobin in sickle cell anemia. Hemoglobin. 2001 May;25(2):195-211.
7. Ingram VM. Separation of the peptide chains of human globin. Nature. 1959 Jun 27;183:1795-98.
8. Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997 Sep 11;337(11):762-9.
9. Steinberg MH. Management of sickle cell disease. N Engl J Med. 1999 Apr 1;340(13):1021-30.
10. Platt OS, Thorington BD, Brambilla DJ, et al. Pain in sickle cell disease. Rates and risk factors. N Engl J Med. 1991 Jul 4;325(1):11-6.
11. Williams TN. Human red blood cell polymorphisms and malaria. Curr Opin Microbiol. 2006 Aug;9(4):388-94.
12. Aidoo M, Terlouw DJ, Kolczak MS, et al. Protective effects of the sickle cell gene against malaria morbidity and mortality. Lancet. 2002 Apr 13; 359(9314):1311-2.
13. Williams TN, Mwangi TW, Wambua S, et al. Negative epistasis between the malaria-protective effects of alpha?-thalassemia and the sickle cell trait. Nat Genet. 2005 Nov;37(11):1253-7.
14. Serjeant GR. Natural history and determinants of clinical severity of sickle cell disease. Curr Opin Hematol. 1995 Mar;2(2):103-8.
15. Steinberg MH. Review: sickle cell disease: present and future treatment. Am J Med Sci. 1996 Oct;312(4):166-74.
16. Noguchi CT, Dover GJ, Rodgers GP, et al. Alpha thalassemia changes erythrocyte heterogeneity in sickle cell disease. J Clin Invest. 1985 May;75(5):1632-7.
17. Steinberg MH, West MS, Gallagher D, Mentzer W. Effects of glucose-6-phosphate dehydrogenase deficiency upon sickle cell anemia. Blood. 1988 Mar;71(3):748-52.
18. Kimmick G, Owen J. Rhabdomyolysis and hemolysis associated with sickle cell trait and glucose-6-phosphate dehydrogenase deficiency. South Med J. 1996 Nov;89(11):1097-8.
19. Cohen-Solal M, Prehu C, Wajcman H, et al. A new sickle cell disease phenotype associating Hb S trait, severe pyruvate kinase deficiency (PK Conakry), and an alpha2 globin gene variant (Hb Conakry). Br J Haematol. 1998 Dec;103(4):950-6.
20. Warkentin TE, Barr RD, Ali MA, Mohandas N. Recurrent acute splenic sequestration crisis due to interacting genetic defects: hemoglobin SC disease and hereditary spherocytosis. Blood. 1990 Jan 1;75(1):266-70.
21. Yang YM, Donnell C, Wilborn W, et al. Splenic sequestration associated with sickle cell trait and hereditary spherocytosis. Am J Hematol. 1992 Jun;40(2):110-6.
22. Adekile AD. Mild-phenotype sickle cell disease: molecular basis, clinical presentation and management recommendations. CURRENT PAEDIATRICS. 2005 February;15(1):57-61.
23. Sebastiani P, Nolan VG, Baldwin CT, et al. A network model to predict the risk of death in sickle cell disease. Blood. 2007 Oct 1;110(7):2727-35.
24. Steinberg MH, Ballas SK, Brunson CY, Bookchin R. Sickle cell anemia in septuagenarians. Blood. 1995 Nov 15;86(10):3997-8.
25. Hebbel RP, Vercellotti GM. The endothelial biology of sickle cell disease. J Lab Clin Med. 1997 Mar;129(3):288-93.
26. Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995 May 18;332(20):1317-22.
27. Dover GJ, Chang VT, Boyer SH, Serjeant GR, Antonarakis S, Higgs DR. The cellular basis for different fetal hemoglobin levels among sickle cell individuals with two, three, and four alpha-globin genes. Blood. 1987 Jan;69(1):341-4.
28. Ofori-Acquah SF, Lalloz MR, Serjeant G, Layton DM. Dominant influence of gamma-globin promoter polymorphisms on fetal haemoglobin expression in sickle cell disease. Cell Mol Biol (Noisy-le-grand). 2004 Feb; 50(1):35-42.
29. Wyszynski DF, Baldwin CT, Cleves MA, et al. Polymorphisms near a chromosome 6q QTL area are associated with modulation of fetal hemoglobin levels in sickle cell anemia. Cell Mol Biol (Noisy-le-grand). 2004 Feb;50(1):23-33.
30. Rucknagel DL, Hanash SH, Sing CF, Winter WP, Whitten CF, Prasad AS. Age and sex effects on hemoglobin F in sickle cell anemia. In: Cellular and Molecular Regulation of Hemoglobin Switching. In: Nienhuis GSAW, ed. New York: Grune and Stratton; 1979:107-18.
31. Morris J, Dunn D, Beckford M, et al. The haematology of homozygous sickle cell disease after the age of 40 years. Br J Haematol. 1991 Mar;77(3):382-5.
32. Dover GJ, Boyer SH. The cellular distribution of fetal hemoglobin: normal adults and hemoglobinopathies. Tex Rep Biol Med. 1980;40:43-54.
33. Nagel RL, Labie D. DNA haplotypes and the beta s globin gene. Prog Clin Biol Res. 1989;316B:371-93.
34. Nagel RLS, M.H. Genetics of the bS gene: origins, epidemiology, and epistasis. In: Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. In: MH. Steinberg BGF, DR. Higgs and RL. Nagel, ed. Cambridge: Cambridge University Press; 2001:711-55.
35. Labie D, Pagnier J, Lapoumeroulie C, et al. Common haplotype dependency of high G gamma-globin gene expression and high Hb F levels in betathalassemia and sickle cell anemia patients. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2111-4.
36. Nagel RL, Fabry ME, Pagnier J, et al. Hematologically and genetically distinct forms of sickle cell anemia in Africa. The Senegal type and the Benin type. N Engl J Med. 1985 Apr 4;312(14):880-4.
37. Steinberg MH, Hsu H, Nagel RL, et al. Gender and haplotype effects upon hematological manifestations of adult sickle cell anemia. Am J Hematol. 1995 Mar;48(3):175-81.
38. Bakanay SM, Dainer E, Clair B, et al. Mortality in sickle cell patients on hydroxyurea therapy. Blood. 2005 Jan 15;105(2):545-7.
39. Dover GJ, Smith KD, Chang YC, et al. Fetal hemoglobin levels in sickle cell disease and normal individuals are partially controlled by an X-linked gene located at Xp22.2. Blood. 1992 Aug 1;80(3):816-24.
40. Thein SL, Sampietro M, Rohde K, et al. Detection of a major gene for heterocellular hereditary persistence of fetal hemoglobin after accounting for genetic modifiers. Am J Hum Genet. 1994 Feb;54(2):214-28.
41. Chang YC, Smith KD, Moore RD, Serjeant GR, Dover GJ. An analysis of fetal hemoglobin variation in sickle cell disease: the relative contributions of the X-linked factor, beta-globin haplotypes, alpha-globin gene number, gender, and age. Blood. 1995 Feb 15;85(4):1111-7.
42. Garner C, Mitchell J, Hatzis T, Reittie J, Farrall M, Thein SL. Haplotype mapping of a major quantitative-trait locus for fetal hemoglobin production, on chromosome 6q23. Am J Hum Genet. 1998 Jun;62(6):1468-74.
43. Close J, Game L, Clark B, Bergounioux J, Gerovassili A, Thein SL. Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a quantitative trait locus for fetal hemoglobin expression in adults. BMC Genomics. 2004 May 31;5(1):33.
44. Garner CP, Tatu T, Best S, Creary L, Thein SL. Evidence of genetic interaction between the beta-globin complex and chromosome 8q in the expression of fetal hemoglobin. Am J Hum Genet. 2002 Mar;70(3):793-99.
45. Garner C, Silver N, Best S, et al. Quantitative trait locus on chromosome 8q influences the switch from fetal to adult hemoglobin. Blood. 2004 Oct 1; 104(7):2184-6.
46. Thein SL, Menzel S, Peng X, et al. Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults. Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11346-51.
47. Garner C, Tatu T, Reittie JE, et al. Genetic influences on F cells and other hematologic variables: a twin heritability study. Blood. 2000 Jan 1; 95(1):342-6.
48. Ma Q, Wyszynski DF, Farrell JJ, et al. Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea. Pharmacogenomics J. 2007 Dec;7(6):386-94.
49. Gladwin MT, Schechter AN, Shelhamer JH, Ognibene FP. The acute chest syndrome in sickle cell disease. Possible role of nitric oxide in its pathophysiology and treatment. Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1368-76.
50. Powars D, Wilson B, Imbus C, Pegelow C, Allen J. The natural history of stroke in sickle cell disease. Am J Med. 1978 Sep;65(3):461-71.
51. Ohene-Frempong K, Weiner SJ, Sleeper LA, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood. Jan 1 1998;91(1):288-94.
52. Hassan A, Markus HS. Genetics and ischaemic stroke. Brain. 2000 Sep;123 (Pt 9):1784-812.
53. Laine M, Salmelin R, Helenius P, Marttila R. Brain activation during reading in deep dyslexia: an MEG study. J Cogn Neurosci. 2000 Jul;12(4):622-34.
54. Hademenos GJ, Alberts MJ, Awad I, et al. Advances in the genetics of cerebrovascular disease and stroke. Neurology. 2001 Apr 24;56(8):997-1008.
55. Matarin M, Brown WM, Scholz S, et al. A genome-wide genotyping study in patients with ischaemic stroke: initial analysis and data release. Lancet Neurol. 2007 May;6(5):414-20.
56. Adams RJ, Kutlar A, McKie V, et al. Alpha thalassemia and stroke risk in sickle cell anemia. Am J Hematol. 1994 Apr;45(4):279-82.
57. Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994 Jun 9; 330(23):1639-44.
58. Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998 Jul 2; 339(1):5-11.
59. Driscoll MC, Hurlet A, Styles L, et al. Stroke risk in siblings with sickle cell anemia. Blood. 15 2003 Mar;101(6):2401-4.
60. Hoppe C, Klitz W, Noble J, Vigil L, Vichinsky E, Styles L. Distinct HLA associations by stroke subtype in children with sickle cell anemia. Blood. 2003 Apr 1;101(7):2865-9.
61. Hoppe C, Klitz W, Cheng S, et al. Gene interactions and stroke risk in children with sickle cell anemia. Blood. 2004 Mar 15;103(6):2391-6.
62. Styles LA, Aarsman AJ, Vichinsky EP, Kuypers FA. Secretory phospholipase A(2) predicts impending acute chest syndrome in sickle cell disease. Blood. 2000 Nov 1;96(9):3276-8.
63. Hoppe C, Klitz W, D'Harlingue K, et al. Confirmation of an association between the TNF(-308) promoter polymorphism and stroke risk in children with sickle cell anemia. Stroke. 2007 Aug;38(8):2241-6.
64. Taylor JGt, Tang DC, Savage SA, et al. Variants in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease. Blood. 2002 Dec 15; 100(13):4303-9.
65. Kutlar A BD, Clair B, Haghighat A, et al. Candidate Gene Polymorphisms and Their Association with TCD Velocities in Children with Sickle Cell Disease. ASH. Atlanta GA USA: Blood; Volume 110, issue 11;2007.
66. Sebastiani P, Ramoni MF, Nolan V, Baldwin CT, Steinberg MH. Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia. Nat Genet. 2005 Apr;37(4):435-40.
67. Zee RY, Cook NR, Cheng S, et al. Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis. Hum Mol Genet. Feb 15 2004;13(4):389-96.
68. Lauritzen SLS, N.A. Graphical models for genetic analysis. Statist Sci. 2004;18:489-514.
69. Romana M, Diara JP, Doumbo L, et al. Angiotensinogen gene associated polymorphisms and risk of stroke in sickle cell anemia: Additional data supporting an association. Am J Hematol. 2004 Jul;76(3):310-11.
70. Steinberg MH, Voskaridou E, Kutlar A, et al. Concordant fetal hemoglobin response to hydroxyurea in siblings with sickle cell disease. Am J Hematol. 2003 Feb;72(2):121-6.
71. Kahn MJ, Scher C, Rozans M, Michaels RK, Leissinger C, Krause J. Factor V Leiden is not responsible for stroke in patients with sickling disorders and is uncommon in African Americans with sickle cell disease. Am J Hematol. 1997 Jan;54(1):12-5.
72. Andrade FL, Annichino-Bizzacchi JM, Saad ST, Costa FF, Arruda VR. Prothrombin mutant, factor V Leiden, and thermolabile variant of methylenetetrahydrofolate reductase among patients with sickle cell disease in Brazil. Am J Hematol. 1998 Sep;59(1):46-50.
73. Liesner R, Mackie I, Cookson J, et al. Prothrombotic changes in children with sickle cell disease: relationships to cerebrovascular disease and transfusion. Br J Haematol. 1998 Dec;103(4):1037-44.
74. Setty BN, Stuart MJ, Dampier C, Brodecki D, Allen JL. Hypoxaemia in sickle cell disease: biomarker modulation and relevance to pathophysiology. Lancet. 2003 Nov 1;362(9394):1450-5.
75. Milner PF, Kraus AP, Sebes JI, et al. Sickle cell disease as a cause of osteonecrosis of the femoral head. N Engl J Med. 1991 Nov 21; 325(21):1476-81.
76. Kutlar A, Kutlar F, Turker I, Tural C. The methylene tetrahydrofolate reductase (C677T) mutation as a potential risk factor for avascular necrosis in sickle cell disease. Hemoglobin. 2001 May;25(2):213-7.
77. Moreira Neto F, Lourenco DM, Noguti MA, et al. The clinical impact of MTHFR polymorphism on the vascular complications of sickle cell disease. Braz J Med Biol Res. 2006 Oct;39(10):1291-5.
78. Adekile AD, Kutlar F, Haider MZ, Kutlar A. Frequency of the 677 C->T mutation of the methylenetetrahydrofolate reductase gene among Kuwaiti sickle cell disease patients. Am J Hematol. 2001 Apr; 66(4):263-6.
79. De Castro L RH, Howe JG, Smith BR. Thrombophilic genotypes do not adversely affect the course of sickle cell disease (SCD). Blood. 1998;92(Suppl):161a.
80. Zimmerman SA, Ware RE. Inherited DNA mutations contributing to thrombotic complications in patients with sickle cell disease. Am J Hematol. 1998 Dec;59(4):267-72.
81. Baldwin C, Nolan VG, Wyszynski DF, et al. Association of klotho, bone morphogenic protein 6, and annexin A2 polymorphisms with sickle cell osteonecrosis. Blood. 2005 Jul 1;106(1):372-5.
82. Sharan K, Surrey S, Ballas S, et al. Association of T-786C eNOS gene polymorphism with increased susceptibility to acute chest syndrome in females with sickle cell disease. Br J Haematol. 2004 Jan;124(2):240-3.
83. Grasemann H, Ratjen F. Gender-specific disease modification by NOS3. Br J Haematol. 2004 Jul;126(1):160; author reply 161.
84. Sullivan KJ, Kissoon N, Duckworth LJ, et al. Low exhaled nitric oxide and a polymorphism in the NOS I gene is associated with acute chest syndrome. Am J Respir Crit Care Med. 2001 Dec 15;164(12):2186-90.
85. Chaar V, Tarer V, Etienne-Julan M, Diara JP, Elion J, Romana M. ET-1 and ecNOS gene polymorphisms andsusceptibility to acute chest syndrome and painful vaso-occlusive crises in children with sickle cell anemia. Haematologica. 2006 Sep;91(9):1277-8.
86. Styles LA, Schalkwijk CG, Aarsman AJ, Vichinsky EP, Lubin BH, Kuypers FA. Phospholipase A2 levels in acute chest syndrome of sickle cell disease. Blood. 1996 Mar 15;87(6):2573-8.
87. Nolan VG, Baldwin C, Ma Q, et al. Association of single nucleotide polymorphisms in klotho with priapism in sickle cell anaemia. Br J Haematol. 2005 Jan;128(2):266-72.
88. Elliott L, Ashley-Koch AE, De Castro L, et al. Genetic polymorphisms associated with priapism in sickle cell disease. Br J Haematol. 2007 May;137(3):262-7.
89. Koshy M, Entsuah R, Koranda A, et al. Leg ulcers in patients with sickle cell disease. Blood. 1989 Sep;74(4):1403-8.
90. Clare A, FitzHenley M, Harris J, Hambleton I, Serjeant GR. Chronic leg ulceration in homozygous sickle cell disease: the role of venous incompetence. Br J Haematol. 2002 Nov;119(2):567-571.
91. Akinyanju O, Akinsete I. Leg ulceration in sickle cell disease in Nigeria. Trop Geogr Med. 1979 Mar;31(1):87-91.
92. Knox-Macaulay HH. Sickle cell disease in Sierra Leone: a clinical and haematological analysis in older children and adults. Ann Trop Med Parasitol. 1983 Aug;77(4):411-9.
93. Durosinmi MA, Gevao SM, Esan GJ. Chronic leg ulcers in sickle cell disease: experience in Ibadan, Nigeria. Afr J Med Med Sci. 1991 Mar;20(1):11-4.
94. Nolan VG, Ma Q, Cohen HT, et al. Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B. Am J Hematol. 2007 Mar;82(3):179-84.
95. Lammert F, Matern S. The genetic background of cholesterol gallstone formation: an inventory of human lithogenic genes. Curr Drug Targets Immune Endocr Metabol Disord. 2005 Jun;5(2):163-70.
96. Lammert F, Sauerbruch T. Mechanisms of disease: the genetic epidemiology of gallbladder stones. Nat Clin Pract Gastroenterol Hepatol. 2005 Sep; 2(9):423-33.
97. Lammert F, Wang DQ. New insights into the genetic regulation of intestinal cholesterol absorption. Gastroenterology. 2005 Aug;129(2):718-34.
98. Bosma PJ, Chowdhury JR, Bakker C, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med. 1995 Nov 2;333(18):1171-5.
99. Monaghan G, Ryan M, Seddon R, Hume R, Burchell B. Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert's syndrome. Lancet. 1996 Mar 2;347(9001):578-81.
100. Beutler E, Gelbart T, Demina A. Racial variability in the UDPglucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci U S A. 1998 Jul 7; 95(14):8170-4.
101. Passon RG, Howard TA, Zimmerman SA, Schultz WH, Ware RE. Influence of bilirubin uridine diphosphate-glucuronosyltransferase 1A promoter polymorphisms on serum bilirubin levels and cholelithiasis in children with sickle cell anemia. J Pediatr Hematol Oncol. 2001 Oct;23(7):448-51.
102. Fertrin KY, Melo MB, Assis AM, Saad ST, Costa FF. UDPglucuronosyltransferase 1 gene promoter polymorphism is associated with increased serum bilirubin levels and cholecystectomy in patients with sickle cell anemia. Clin Genet. 2003 Aug;64(2):160-2.
103. Haverfield EV, McKenzie CA, Forrester T, et al. UGT1A1 variation and gallstone formation in sickle cell disease. Blood. 2005 Feb 1;105(3):968-72.
104. Heeney MM, Howard TA, Zimmerman SA, Ware RE. UGT1A promoter polymorphisms influence bilirubin response to hydroxyurea therapy in sickle cell anemia. J Lab Clin Med. 2003 Apr;141(4):279-82.
105. Kinney TR, Helms RW, O'Branski EE, et al. Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. Blood. 1999 Sep 1;94(5):1550-4.
106. Chaar V, Keclard L, Diara JP, et al. Association of UGT1A1 polymorphism with prevalence and age at onset of cholelithiasis in sickle cell anemia. Haematologica. 2005 Feb;90(2):188-99.
107. Kalotychou V, Antonatou K, Tzanetea R, Terpos E, Loukopoulos D, Rombos Y. Analysis of the A(TA)(n)TAA configuration in the promoter region of the UGT1 A1 gene in Greek patients with thalassemia intermedia and sickle cell disease. Blood Cells Mol Dis. 2003 Jul-Aug;31(1):38-42.
108. Adewoye AH, Nolan VG, Ma Q, et al. Association of polymorphisms of IGF1R and genes in the transforming growth factor- beta/bone morphogenetic protein pathway with bacteremia in sickle cell anemia. Clin Infect Dis. 2006 Sep 1;43(5):593-8.
109. Tamouza R, Neonato MG, Busson M, et al. Infectious complications in sickle cell disease are influenced by HLA class II alleles. Hum Immunol. 2002 Mar;63(3):194-99.
110. Tamouza R, Busson M, Fortier C, et al. HLA-E*0101 allele in homozygous state favors severe bacterial infections in sickle cell anemia. Hum Immunol. 2007 Oct;68(10):849-53.
111. Costa RN, Conran N, Albuquerque DM, Soares PH, Saad ST, Costa FF. Association of the G-463A myeloperoxidase polymorphism with infection in sickle cell anemia. Haematologica. 2005 Jul;90(7):977-9.
112. Thomas AN, Pattison C, Serjeant GR. Causes of death in sickle-cell disease in Jamaica. Br Med J (Clin Res Ed). 1982 Aug 28-Sep 4;285(6342):633-5.
113. McKie KT, Hanevold CD, Hernandez C, Waller JL, Ortiz L, McKie KM. Prevalence, prevention, and treatment of microalbuminuria and proteinuria in children with sickle cell disease. J Pediatr Hematol Oncol. 2007 Mar; 29(3):140-4.
114. Thompson J, Reid M, Hambleton I, Serjeant GR. Albuminuria and renal function in homozygous sickle cell disease: observations from a cohort study. Arch Intern Med. 2007 Apr 9;167(7):701-8.
115. Ashley-Koch AE, Elliott L, Kail ME, et al. Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. Blood. 2008 Jun 15;111(12):5721-6.
116. Yildiz P, Oflaz H, Cine N, Erginel-Unaltuna N, Erzengin F, Yilmaz V. Gene polymorphisms of endothelial nitric oxide synthase enzyme associated with pulmonary hypertension in patients with COPD. Respir Med. 2003 Dec;97(12):1282-8.
117. Yildiz P, Oflaz H, Cine N, et al. Endothelial dysfunction in patients with asthma: the role of polymorphisms of ACE and endothelial NOS genes. J Asthma. 2004 Apr;41(2):159-66.
118. Hines PC, Zen Q, Burney SN, et al. Novel epinephrine and cyclic AMPmediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion. Blood. 2003 Apr 15;101(8):3281-7.
119. Zennadi R, Hines PC, De Castro LM, Cartron JP, Parise LV, Telen MJ. Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions. Blood. 2004 Dec 1;104(12):3774-81.
120. Zennadi R, Moeller BJ, Whalen EJ, et al. Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo. Blood. 2007 Oct 1;110(7):2708-17.
121. Eyler CE, Jackson T, Elliott LE, et al. beta(2)-Adrenergic receptor and adenylate cyclase gene polymorphisms affect sickle red cell adhesion. Br J Haematol. 2008 Apr;141(1):105-8.
122. Steinberg MH, Adewoye AH. Modifier genes and sickle cell anemia. Curr Opin Hematol. 2006 May;13(3):131-6.
123. Steinberg MH, Nagel RL, Lawrence C, et al. Beta-globin gene haplotype in Hb SC disease. Am J Hematol. 1996 Jul;52(3):189-91.
124. Wierenga KJ, Hambleton IR, Lewis NA. Survival estimates for patients with homozygous sickle-cell disease in Jamaica: a clinic-based population study. Lancet. 2001 Mar 3;357(9257):680-3.
125. Pagnier J, Mears JG, Dunda-Belkhodja O, et al. Evidence for the multicentric origin of the sickle cell hemoglobin gene in Africa. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1771-3.
126. Nagel RL, Fabry ME. The many pathophysiologies of sickle cell anemia. Am J Hematol. 1985 Oct;20(2):195-9.
127. Kurnit DM. Evolution of sickle variant gene. Lancet. 1979 Jan;1(8107):104.
128. Angastiniotis M, Modell B, Englezos P, Boulyjenkov V. Prevention and control of haemoglobinopathies. Bull World Health Organ. 1995;73(3):375-86.
129. Ofori-Acquah SF OFK. Beyond National Borders: A global perspective on advances in sickle cell disease research and management, and new challenges in the genome era. In: Pace B, ed. Renaissance of Sickle Cell Disease Research in the Genome Era. London: Imperial College Press; 2007:333-45.
130. Barbujani G, Magagni A, Minch E, Cavalli-Sforza LL. An apportionment of human DNA diversity. Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4516-9.
131. Rosenberg NA, Pritchard JK, Weber JL, et al. Genetic structure of human populations. Science. 2002 Dec 20;298(5602):2381-5.
132. Hibbert JM, Creary MS, Gee BE, Buchanan ID, Quarshie A, Hsu LL. Erythropoiesis and myocardial energy requirements contribute to the hypermetabolism of childhood sickle cell anemia. J Pediatr Gastroenterol Nutr. 2006 Nov;43(5):680-7.
133. Archer DR, Stiles JK, Newman GW, et al. C-reactive protein and interleukin-6 are decreased in transgenic sickle cell mice fed a high protein diet. J Nutr. 2008 Jun;138(6):1148-52.
134. Sinha S, Mishra SK, Sharma S, et al. Polymorphisms of TNF-enhancer and gene for FcgammaRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population. Malar J. 2008;7:13.
135. Timmann C, Evans JA, Konig IR, et al. Genome-wide linkage analysis of malaria infection intensity and mild disease. PLoS Genet. 2007 Mar 23; 3(3):e48.
136. Marquet S, Doumbo O, Cabantous S, et al. A functional promoter variant in IL12B predisposes to cerebral malaria. Hum Mol Genet. 2008 Jul 15; 17(14):2190-5.
137. Soares-Souza GB, Tarazona-Santos E, Chanock SJ. Characterization of a candidate locus for malaria susceptibility in human populations: a (TA)n microsatellite in the promoter region of the CYBB gene, the gp91 phox subunit of the NADPH oxidase. Int J Immunogenet. 2008 Apr;35(2):107-9.
138. Cox SE, Doherty C, Atkinson SH, et al. Haplotype association between haptoglobin (Hp2) and Hp promoter SNP (A-61C) may explain previous controversy of haptoglobin and malaria protection. PLoS ONE. 2007;2(4):e362.
139. Magi R, Pfeufer A, Nelis M, Montpetit A, Metspalu A, Remm M. Evaluating the performance of commercial whole-genome marker sets for capturing common genetic variation. BMC Genomics. 2007;8:159.
140. Weatherall MW, Higgs DR, Weiss H, Weatherall DJ, Serjeant GR. Phenotype/genotype relationships in sickle cell disease: a pilot twin study. Clin Lab Haematol. 2005 Dec;27(6):384-90.
141. Nagel RL, Fabry ME. Sickle cell anemia as a multigenetic disease: new insights into the mechanism of painful crisis. Prog Clin Biol Res. 1984;165:93-102.
142. Lettre G, Sankaran VG, Bezerra MA, et al. DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11869-74.
143. Sebastiani P, Wang L, Nolan VG, et al. Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations. Am J Hematol. 2008 Mar;83(3):189-95.
144. Uda M, Galanello R, Sanna S, et al. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc Natl Acad Sci U S A. 2008 Feb 5; 105(5):1620-5.
145. Hoppe B, Heymann GA, Schoenemann C, Nagy M, Kiesewetter H, Salama A. Description of a novel HLA-B allele, B*5613, identified during HLA-typing using sequence-specific oligonucleotide hybridization and sequence-specific amplification. Tissue Antigens. 2004 Nov;64(5):616-8.
146. Styles LA, Hoppe C, Klitz W, Vichinsky E, Lubin B, Trachtenberg E. Evidence for HLA-related susceptibility for stroke in children with sickle cell disease. Blood. 2000 Jun 1;95(11):3562-7.
147. Tang DC, Prauner R, Liu W, et al. Polymorphisms within the angiotensinogen gene (GT-repeat) and the risk of stroke in pediatric patients with sickle cell disease: a case-control study. Am J Hematol. 2001 Nov;68(3):164-9.
148. Nolan VG, Adewoye A, Baldwin C, et al. Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF-beta/ BMP pathway. Br J Haematol. 2006 Jun;133(5):570-8.