Genetic modifiers of sickle cell disease

Hemoglobin

Volumn 35, Issue 5-6, 2011, Pages 589-606

  Thein, Swee Lay ^a,b  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b KING'S COLLEGE HOSPITAL NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

Genetic association studies; Genome wide association studies (GWAS); Sickle cell disease

Indexed keywords

BILIRUBIN; ERYTHROID KRUPPEL LIKE FACTOR; GLUCURONOSYLTRANSFERASE 1A1; HEMOGLOBIN F; LACTATE DEHYDROGENASE; LACTATE DEHYDROGENASE ISOENZYME;

ALPHA THALASSEMIA; BENIN; BETA THALASSEMIA; BILIRUBIN BLOOD LEVEL; BONE NECROSIS; CENTRAL AFRICAN REPUBLIC; DNA MODIFICATION; GALLSTONE; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE MAPPING; GENETIC ASSOCIATION; GENETIC REGULATION; GENETIC VARIABILITY; GENOTYPE PHENOTYPE CORRELATION; GEOGRAPHIC DISTRIBUTION; GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY; HEMODILUTION; HEMOGLOBIN BLOOD LEVEL; HEMOLYSIS; HETEROZYGOTE; HOMOZYGOTE; HUMAN; INDIA; KIDNEY DYSFUNCTION; LEG ULCER; MEAN CORPUSCULAR HEMOGLOBIN; MEAN CORPUSCULAR VOLUME; NEGRO; PAIN; POLYMERIZATION; PRIAPISM; PULMONARY HYPERTENSION; QUANTITATIVE GENETICS; RETICULOCYTE COUNT; RETINOPATHY; REVIEW; SENEGAL; SICKLE CELL ANEMIA; SINGLE NUCLEOTIDE POLYMORPHISM; STROKE; VASCULAR DISEASE;

ANEMIA, SICKLE CELL; ANIMALS; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS;

EID: 81055147553     PISSN: 03630269     EISSN: 1532432X     Source Type: Journal    
DOI: 10.3109/03630269.2011.615876     Document Type: Review

References (131)

1. Pauling L, Itano HA, Singer SJ, et al. Sickle cell anemia: a molecular disease. Science. 1949;110(2865):543-548.
2. Ingram VM. Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin. Nature. 1957;180(4581):326-328.
3. Goldstein J, Konigsberg W, Hill RJ. The structure of human hemoglobin: VI. The sequence of amino acids in the tryptic peptides of the β chain. J Biol Chem. 1963;238(6):2016-2027.
4. Smith-Whitley K, Pace BS. Sickle cell disease: a phenotypic patchwork. In: Pace BS, Ed. Renaissance of Sickle Cell Disease Research in the Genome Era (1st ed.). London: Imperial College Press. 2007:45-67.
5. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018-2031.
6. Driscoll MC, Hurlet A, Styles L, et al. Stroke risk in siblings with sickle cell anemia. Blood. 2003;101(6):2401-2404. (Pubitemid 36302088)
7. Steinberg MH, Voskaridou E, Kutlar A, et al. Concordant fetal hemoglobin response to hydroxyurea in siblings with sickle cell disease. Am J Hematol. 2003;72(2):121-126. (Pubitemid 36164347)
8. Steinberg MH. Determinants of fetal hemoglobin response to hydroxyurea. Semin Hematol. 1997;34(3, Suppl 3):8-14.
9. Kumkhaek C, Taylor JG 6th, Zhu J, et al. Fetal haemoglobin response to hydroxycarbamide treatment and sar1a promoter polymorphisms in sickle cell anaemia. Br J Haematol. 2008;141(2): 254-259.
10. Ma Q, Wyszynski DF, Farrell JJ, et al. Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea. Pharmacogenomics J. 2007;7(6):386-394. (Pubitemid 350187450)
11. Amin BR, Bauersachs RM, Meiselman HJ, et al. Monozygotic twins with sickle cell anemia and discordant clinical courses: clinical and laboratory studies. Hemoglobin. 1991;15(4):247-256.
12. Joishy SK, Griner PF, Rowley PT. Sickle β-thalassemia: identical twins differing in severity implicate nongenetic factors influencing course. Am J Hematol. 1976;1(1):23-33.
13. Weatherall MW, Higgs DR, Weiss H, et al. Phenotype/genotype relationships in sickle cell disease: a pilot twin study. Clin Lab Haematol. 2005;27(6):384-390. (Pubitemid 41784348)
14. Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28(10):1057-1068.
15. Jirtle RL, Skinner MK. Environmental epigenomics and disease susceptibility. Nat Rev Genet. 2007;8(4):253-262. (Pubitemid 46439287)
16. Noguchi C, Schechter AN, Rodgers GP. Sickle cell disease pathophysiology. In:Higgs DR,Weatherall DJ, Eds. Baillière's Clinical Haematology: The Haemoglobinopathies. Vol. 6. London: Baillière Tindall. 1993:57-91. (Pubitemid 23144094)
17. Bonham VL, Dover GJ, Brody LC. Screening student athletes for sickle cell trait-a social and clinical experiment. N Engl J Med. 2010;363(11):997-999.
18. Kark JA, Posey DM, Schumacher HR, et al. Sickle-cell trait as a risk factor for sudden death in physical training. N Engl J Med. 1987;317(13):781- 787. (Pubitemid 17133357)
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 α2 globin gene variant (Hb Conakry). Br J Haematol. 1998;103(4):950-956. (Pubitemid 29012629)
20. Alli N, Coetzee M, Louw V, et al. Sickle cell disease in a carrier with pyruvate kinase deficiency.Hematology. 2008;13(6):369-372.
21. Yang YM, Donnell C, Wilborn W, et al. Splenic sequestration associated with sickle cell trait and hereditary spherocytosis. Am J Hematol. 1992;40(2):110-116.
22. Vasavda N, Menzel S, Kondaveeti S, et al. The linear effects of α-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease. Br J Haematol. 2007;138(2): 263-270. (Pubitemid 46976326)
23. FabryME. Molecular genetics of the human globin genes. In: Steinberg MH, Forget BG, Higgs DR, Nagel RL, Eds. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge: Cambridge University Press. 2001:910-940.
24. Flint J, Mott R. Applying mouse complex-trait resources to behavioural genetics. Nature. 2008;456(7223):724-727.
25. Blouin MJ, Beauchemin H, Wright A, et al. Genetic correction of sickle cell disease: insights using transgenic mouse models. Nat Med. 2000;6(2):177-182. (Pubitemid 30082362)
26. De Franceschi L, Brugnara C, Rouyer-Fessard P, et al. Formation of dense erythrocytes in SAD mice exposed to chronic hypoxia: evaluation of different therapeutic regimens and a combination of oral clotrimazole and magnesium therapies. Blood. 1999;94(12):4307-4313.
27. Pawliuk R, Westerman KA, Fabry ME, et al. Correction of sickle cell disease in transgenic mouse models by gene therapy. Science. 2001;294(5550):2368-2371. (Pubitemid 33140563)
28. Freimer N, Sabatti C. The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology. Nat Genet. 2004;36(10):1045-1051. (Pubitemid 41184462)
29. Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747-753.
30. Manolio TA. Genomewide association studies and assessment of the risk of disease. N Engl J Med. 2010;363(2):166-176.
31. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447(7145):661-678.
32. Craddock N, Hurles ME, Cardin N, et al. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature. 2010;464(7289):713-720.
33. Steinberg MH. Genetic etiologies for phenotypic diversity in sickle cell anemia. ScientificWorld Journal. 2009;9:46-67.
34. Roach JC, Glusman G, Smit AF, et al. Analysis of genetic inheritance in a family quartet by wholegenome sequencing. Science. 2010;328(5978):636-639.
35. Thein SL, Menzel S, Lathrop M, et al. Control of fetal hemoglobin: new insights emerging from genomics and clinical implications. Hum Mol Genet. 2009;18(R2):R216-223.
36. Thein SL, Menzel S. Discovering the genetics underlying foetal haemoglobin production in adults. Br J Haematol. 2009;145(4):455-467.
37. Steinberg MH, Embury SH. α-Thalassemia in blacks: genetic and clinical aspects and interactions with the sickle hemoglobin gene. Blood. 1986;68(5):985-990. (Pubitemid 17186370)
38. Ballas SK. Effect of α-globin genotype on the pathophysiology of sickle cell disease. Pediatr Pathol Mol Med. 2001;20(2):107-121. (Pubitemid 32240557)
39. Embury SH, Dozy AM, Miller J, et al. Concurrent sickle-cell anemia and α-thalassemia: effect on severity of anemia. N Engl J Med. 1982;306(5):270-274. (Pubitemid 12165028)
40. Buchanan GR, DeBaun MR, Quinn CT, et al. Sickle cell disease. Hematology Am Soc Hematol Educ Program. 2004:35-47.
41. Thomas PW, Higgs DR, Serjeant GR. Benign clinical course in homozygous sickle cell disease: a search for predictors. J Clin Epidemiol. 1997;50(2):121-126. (Pubitemid 27129712)
42. Serjeant GR, Higgs DR, Hambleton IR. Elderly survivors with homozygous sickle cell disease. N Engl J Med. 2007;356(6):642-643. (Pubitemid 46220847)
43. Vasavda N, Badiger S, Rees D, et al. The presence of α-thalassaemia trait blunts the response to hydroxycarbamide in patients with sickle cell disease. Br J Haematol. 2008;143(4):589-592.
44. Ataga KI, Smith WR, De Castro LM, et al. Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia. Blood. 2008;111(8):3991-3997.
45. Penman BS, Pybus OG, Weatherall DJ, et al. Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean. Proc Natl Acad Sci USA. 2009;106(50):21242-21246.
46. 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;330(23):1639-1644.
47. Wang WC, Pavlakis SG, Helton KJ, et al. MRI abnormalities of the brain in one-year-old children with sickle cell anemia. Pediatr Blood Cancer. 2008;51(5):643-646.
48. Powars DR,Weiss JN, Chan LS, et al. Is there a threshold level of fetal hemoglobin that ameliorates morbidity in sickle cell anemia. Blood. 1984;63(4):921-926. (Pubitemid 14141316)
49. 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;312(14):880-884. (Pubitemid 15105672)
50. Steinberg MH, Hsu H, Nagel RL, et al. Gender and haplotype effects upon hematological manifestations of adult sickle cell anemia. Am J Hematol. 1995;48(3):175-181.
51. Labie D, Pagnier J, Lapoumeroulie C, et al. Common haplotype dependency of high Gγ-globin gene expression and high Hb F levels in β-thalassemia and sickle cell anemia patients. Proc Natl Acad Sci USA. 1985;82(7):2111-2114. (Pubitemid 15056478)
52. Kulozik AE, Kar BC, Satapathy RK, et al. Fetal hemoglobin levels and βS globin haplotypes in an Indian population with sickle cell disease. Blood. 1987;69(6):1742-1746. (Pubitemid 17091634)
53. 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 β-thalassemia. Proc Natl Acad Sci USA. 2008;105(5):1620-1625. (Pubitemid 351346564)
54. Solovieff N, Milton JN, Hartley SW, et al. 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):1815-1822.
55. Menzel S, Garner C, Gut I, et al. A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15. Nat Genet. 2007;39(10):1197-1199. (Pubitemid 47482679)
56. Craig JE, Rochette J, Fisher CA, et al. Dissecting the loci controlling fetal haemoglobin production on chromosomes 11p and 6q by the regressive approach. Nat Genet. 1996;12(1):58-64. (Pubitemid 26011320)
57. Garner C, Mitchell J, Hatzis T, et al. Haplotype mapping of a major QTL for fetal hemoglobin production on chromosome 6q23. Am J Hum Genet. 1998;62(6):1468-1474. (Pubitemid 28307117)
58. Satterwhite E, Sonoki T, Willis TG, et al. The BCL11 gene family: involvement of BCL11A in lymphoid malignancies. Blood. 2001;98(12):3413-3420.
59. Lettre G, Sankaran VG, Bezerra MA, et al. DNA polymorphisms at the BCL11A, HBS1L-MYB, and β-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proc Natl Acad Sci USA. 2008;105(33):11869-11874.
60. Sedgewick AE, Timofeev N, Sebastiani P, et al. BCL11A is a major Hb F quantitative trait locus in three different populations with β-hemoglobinopathies. Blood Cells Mol Dis. 2008;41(3):255-258.
61. So CC, Song YQ, Tsang ST, et al. The HBS1L-MYB intergenic region on chromosome 6q23 is a quantitative trait locus controlling fetal haemoglobin level in carriers of β-thalassaemia. J Med Genet. 2008;45(11):745-751.
62. Creary LE, Ulug P, Menzel S, et al. Genetic variation on chromosome 6 influences F cell levels in healthy individuals of African descent and Hb F levels in sickle cell patients. PLoS ONE. 2009;4(1):e4218.
63. Galanello R, Sanna S, Perseu L, et al. Amelioration of Sardinian β0 thalassemia by genetic modifiers. Blood. 2009;114(18):3935-3937.
64. Nuinoon M, Makarasara W, Mushiroda T, et al. A genome-wide association identified the common genetic variants influence disease severity in β0-thalassemia/Hemoglobin E. Hum Genet. 2010;127(3):303-314.
65. 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):1390-1392.
66. Borg J, Patrinos GP, Felice AE, et al. Erythroid phenotypes associated with KLF1 mutations. Haematologica. 2011;96(5):635-638.
67. Miller IJ, Bieker JJ. A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family of nuclear proteins. Molec Cell Biol. 1993;13(5):2776-2786. (Pubitemid 23133950)
68. Perkins AC, Sharpe AH, Orkin SH. Lethal β-thalassaemia in mice lacking the erythroid CACCCtranscription factor EKLF. Nature. 1995;375(6529):318-322.
69. Nuez B, Michalovich D, Bygrave A, et al. Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene. Nature. 1995;375(6529):316-318.
70. Borg J, Papadopoulos P, Georgitsi M, et al. Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin. Nat Genet. 2010;42(9):801-805.
71. Singleton BK, Fairweather VSS, Lau W, et al. A novel EKLF mutation in a patient with dyserythropoietic anemia: the first association of EKLF with disease in man. (American Society of Hematology Abstracts, #162). Blood. 2009;114(22):72.
72. Arnaud L, Saison C, Helias V, et al. A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia. Am J Hum Genet. 2010;87(5): 721-727.
73. Satta S, Perseu L, Moi P, et al. Compound heterozygosity for KLF1 mutations associated with remarkable increase of fetal hemoglobin and red cell protoporphyrin. Haematologica. 2011;96(5):767-770.
74. Zhou D, Liu K, Sun CW, et al. KLF1 regulates BCL11A expression and γ- to β-globin gene switching. Nat Genet. 2010;42(9):742-744.
75. Bianchi E, Zini R, Salati S, et al. c-Myb supports erythropoiesis through the transactivation of KLF1 and LMO2 expression. Blood. 2010;116(22):e99-e110.
76. Galarneau G, Palmer CD, Sankaran VG, et al. Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation. Nat Genet. 2010;42(12)1049-1051.
77. Bouanga JC, Mouele R, Prehu C, et al. Glucose-6-phosphate dehydrogenase deficiency and homozygous sickle cell disease in Congo. Hum Hered. 1998;48(4):192-197. (Pubitemid 28362460)
78. Bernaudin F, Verlhac S, Chevret S, et al. G6PD deficiency, absence of α-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia. Blood. 2008;112(10):4314-4317.
79. Rees DC, Lambert C, Cooper E, et al. Glucose 6 phosphate dehydrogenase deficiency is not associated with cerebrovascular disease in children with sickle cell anemia. Blood. 2009;114(3):742-743; author reply 743-744.
80. Steinberg MH, West MS, Gallagher D, et al. Effects of glucose-6-phosphate dehydrogenase deficiency upon sickle cell anemia. Blood. 1988;71(3):748-752.
81. Powars DR, Chan LS, Hiti A, et al. Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore). 2005;84(6):363-376. (Pubitemid 41668935)
82. Kato GJ, Gladwin MT, Steinberg MH. Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev. 2007;21(1):37-47. (Pubitemid 46110926)
83. Ballas SK. Sickle cell anemia with few painful crises is characterized by decreased red cell deformability and increased number of dense cells. Am J Hematol. 1991;36(2):122-130.
84. Alexander N, Higgs D, Dover G, et al. Are there clinical phenotypes of homozygous sickle cell disease? Br J Haematol. 2004;126(4):606-611. (Pubitemid 39093105)
85. Ballas SK. Current issues in sickle cell pain and its management. Hematology Am Soc Hematol Educ Program. 2007:97-105.
86. Passon RG, Howard TA, Zimmerman SA, et al. Influence of bilirubin uridine diphosphateglucuronosyltransferase 1A promoter polymorphisms on serum bilirubin levels and cholelithiasis in children with sickle cell anemia. Am J Pediatr Hematol Oncol. 2001;23(7):448-451. (Pubitemid 33031774)
87. 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;90(2):188-199.
88. Heeney MM, Howard TA, Zimmerman SA, et al. UGT1A promoter polymorphisms influence bilirubin response to hydroxyurea therapy in sickle cell anemia. J Lab Clin Med. 2003;141(4):279-282. (Pubitemid 36432929)
89. Chaar V, Keclard L, Etienne-Julan M, et al. UGT1A1 polymorphism outweighs the modest effect of deletional (-3.7 kb) α-thalassemia on cholelithogenesis in sickle cell anemia. Am J Hematol. 2006;81(5):377-379.
90. Hoppe C, Klitz W, Cheng S, et al. Gene interactions and stroke risk in children with sickle cell anemia. Blood. 2004;103(6):2391-2396. (Pubitemid 38326263)
91. Kutlar A, Brambilla D, Clair B, et al. Candidate gene polymorphisms and their association with TCD velocities in children with sickle cell disease. (American Society of Hematology Abstracts, #429). 2007;110(11):133a.
92. Flanagan JM, Howard TA, Frohlich DM, et al. Validation of genetic predictors for stroke in children with sickle cell anemia. Proceedings of the 52nd American Society of Hematology Annual Meeting, Orlando, FL, USA, 2010 (Abstract 2693, Poster Session).
93. 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;128(2):266-272.
94. Nolan VG, Wyszynski DF, Farrer LA, et al. Hemolysis-associated priapism in sickle cell disease. Blood. 2005;106(9):3264-3267. (Pubitemid 41565928)
95. Elliott L, Ashley-Koch AE, De Castro L, et al. Genetic polymorphisms associated with priapism in sickle cell disease. Br J Haematol. 2007;137(3):262-267. (Pubitemid 46537636)
96. Lustosa Souza CR, Azevedo Shimmoto MM, Vicari P, et al. Klotho polymorphisms and priapism in sickle cell disease. Proceedings of the 52nd American Society of Hematology Annual Meeting, Orlando, FL, USA, 2010 (Abstract 1653, Poster Session).
97. Castro V, Alberto FL, Costa RN, et al. Polymorphism of the human platelet antigen-5 system is a risk factor for occlusive vascular complications in patients with sickle cell anemia. Vox Sang. 2004;87(2):118-123. (Pubitemid 39265460)
98. Zimmerman SA, Ware RE. Inherited DNA mutations contributing to thrombotic complications inpatients with sickle cell disease. Am J Hematol. 1998;59(4):267-272. (Pubitemid 28543614)
99. Kutlar A, Kutlar F, Turker I, et al. The methylene tetrahydrofolate reductase (C677T) mutation as a potential risk factor for avascular necrosis in sickle cell disease. Hemoglobin. 2001;25(2):213-217. (Pubitemid 32660541)
100. Andrade FL, Annichino-Bizzacchi JM, Saad ST, et al. Prothrombin mutant, factor V Leiden, and thermolabile variant of methylenetetrahydrofolate reductase among patients with sickle cell disease in Brazil. Am J Hematol. 1998;59(1):46-50. (Pubitemid 28395006)
101. 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;106(1):372-375. (Pubitemid 40967216)
102. Adewoye AH, Nolan VG, Ma Q, et al. Association of polymorphisms of IGF1R and genes in the transforming growth factor-β/bone morphogenetic protein pathway with bacteremia in sickle cell anemia. Clin Infect Dis. 2006;43(5):593-598. (Pubitemid 44267118)
103. Ulug P, Vasavda N, Awogbade M, et al. Association of sickle avascular necrosis with bone morphogenic protein 6. Ann Hematol. 2009;88(8):803-805.
104. 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-β/BMP pathway. Br J Haematol. 2006;133(5):570-578.
105. Gladwin MT, Sachdev V, Jison ML, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004;350(9):886-895. (Pubitemid 38252536)
106. Taylor JGT, Nolan VG, Mendelsohn L, et al. Chronic hyper-hemolysis in sickle cell anemia: association of vascular complications and mortality with less frequent vasoocclusive pain. PLoS One. 2008;3(5):e2095.
107. 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;111(12):5721-5726.
108. Machado RD, Pauciulo MW, Thomson JR, et al. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet. 2001;68(1):92-102. (Pubitemid 32048364)
109. Martinez-Castaldi C, Nolan VG, Baldwin CT, et al. Association of genetic polymorphisms in the TGF-β pathway with the acute chest syndrome of sickle cell anemia. Proceedings of the 49th American Society of Hematology Annual Meeting, Atlanta, GA, USA, 2007 (Abstract 2247, Poster Session).
110. 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;164(12): 2186-2190. (Pubitemid 34032933)
111. 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;124(2):240-243. (Pubitemid 38122198)
112. Costa RN, Conran N, Albuquerque DM, et al. Association of the G-463A myeloperoxidase polymorphism with infection in sickle cell anemia. Haematologica. 2005;90(7):977-979. (Pubitemid 41020301)
113. Nebor D, Durpes MC, Mougenel D, et al. Association between Duffy antigen receptor for chemokines expression and levels of inflammation markers in sickle cell anemia patients. Clin Immunol. 2010;136(1):116-122.
114. Tamouza R, Neonato MG, Busson M, et al. Infectious complications in sickle cell disease are influenced by HLA class II alleles. Hum Immunol. 2002;63(3):194-199. (Pubitemid 34246052)
115. 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;68(10):849-853. (Pubitemid 47610697)
116. Neonato MG, Lu CY, Guilloud-Bataille M, et al. Genetic polymorphism of the mannose-binding protein gene in children with sickle cell disease: identification of three new variant alleles and relationship to infections. Eur J Hum Genet. 1999;7(6):679-686. (Pubitemid 29424059)
117. Cordero EA, Veit TD, da Silva MA, et al. HLA-G polymorphism influences the susceptibility to HCV infection in sickle cell disease patients. Tissue Antigens. 2009;74(4):308-313.
118. Al-Ola K, Mahdi N, Al-Subaie AM, et al. Evidence for HLA class II susceptible and protective haplotypes for osteomyelitis in pediatric patients with sickle cell anemia. Tissue Antigens. 2008;71(5):453-457. (Pubitemid 351537539)
119. Becton LJ, Kalpatthi RV, Rackoff E, et al. Prevalence and clinical correlates of microalbuminuria in children with sickle cell disease. Pediatr Nephrol. 2010;25(8):1505-1511.
120. Maier-Redelsperger M, Levy P, Lionnet F, et al. Strong association between a new marker of hemolysis and glomerulopathy in sickle cell anemia. Blood Cells Mol Dis. 2010;45(4):289-292.
121. Nebor D, Broquere C, Brudey K, et al. α-Thalassemia is associated with a decreased occurrence and a delayed age-at-onset of albuminuria in sickle cell anemia patients. Blood Cells Mol Dis. 2010;45(2):154-158.
122. Steinberg MH, Adewoye AH. Modifier genes and sickle cell anemia. Curr Opin Hematol. 2006;13(3):131-136.
123. 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;82(3):179-184. (Pubitemid 46363782)
124. Sebastiani P, Solovieff N, Hartley SW, et al. Genetic modifiers of the severity of sickle cell anemia identified through a genome-wide association study. Am J Hematol. 2010;85(1):29-35.
125. Taylor JG 6th, Tang DC, Savage SA, et al. Variants in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease. Blood. 2002;100(13):4303- 4309. (Pubitemid 35429667)
126. 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;38(8):2241-2246. (Pubitemid 47457562)
127. Sebastiani P, Ramoni MF, Nolan V, et al. Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia. Nat Genet. 2005;37(4):435-440.
128. 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;68(3):164-169. (Pubitemid 32983204)
129. Styles L, Hoppe C, Klitz W, et al. Evidence for HLA-related susceptibility for stroke in children with sickle cell disease. Blood. 2000;95(11):3562-3567. (Pubitemid 30428492)
130. Peters KG, Kontos CD, Lin PC, et al. Functional significance of Tie2 signaling in the adult vasculature. Recent Prog Horm Res. 2004;59:51-71.
131. Dossou-Yovo OP, Zaccaria I, Benkerrou M, et al. Effects of RANTES and MBL2 gene polymorphisms in sickle cell disease clinical outcomes: association of the g.In1.1T>C RANTES variant with protection against infections. Am J Hematol. 2009;84(6):378-380.