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PMID: 20507315 Published · ppublish English Journal Article Multicenter Study Research Support, N.I.H., Extramural

Association of G6PD with lower haemoglobin concentration but not increased haemolysis in patients with sickle cell anaemia.

British journal of haematology ·Vol. 150 ·No. 2 ·2010-07-00 ·Pages 218-25

Nouraie M, Reading NS, Campbell A, Minniti CP, Rana SR, Luchtman-Jones L, Kato GJ, Gladwin MT, Castro OL, Prchal JT, Gordeuk VR

Abstract

The genetic bases of the highly variable degrees of anaemia and haemolysis in persons with Hb SS are not fully known, but several studies have indicated that G6PD deficiency is not a factor. The G6PD(202A) and G6PD(376G) alleles and alpha-thalassaemia were determined by molecular genetic testing in 261 children and adolescents with Hb SS in a multicentre study. G6PD(202A,376G) (G6PD A-) was defined as hemizygosity for both alleles in males and homozygosity in females. Among the participants 41% were receiving hydroxycarbamide. The prevalence of G6PD(202A,376G) was 13.6% in males and 3.3% in females with an overall prevalence of 8.7%. G6PD(202A,376G) was associated with a 10 g/l decrease in haemoglobin concentration (P = 0.008) but not with increased haemolysis as measured by lactate dehydrogenase, bilirubin, aspartate-aminotransferase, reticulocyte count or a haemolytic component derived from these markers (P > 0.09). Similar results were found within a sub-group of children who were not receiving hydroxycarbamide. By comparison, single and double alpha-globin deletions were associated with progressively higher haemoglobin concentrations (P = 0.005 for trend), progressively lower values for haemolytic component (P = 0.007), and increased severe pain episodes (P < 0.001). In conclusion, G6PD(202A,376G) may be associated with lower haemoglobin concentration in sickle cell anaemia by a mechanism other than increased haemolysis.

MeSH Terms
Adolescent Alleles Anemia, Sickle Cell/blood,complications,drug therapy,genetics Antisickling Agents/therapeutic use Child Child, Preschool Female Genotype Glucosephosphate Dehydrogenase/genetics Glucosephosphate Dehydrogenase Deficiency/blood,complications,genetics Hemoglobins/analysis Hemolysis/genetics Humans Hydroxyurea/therapeutic use Male Phenotype Young Adult alpha-Thalassemia/blood
Chemicals
Antisickling Agents Hemoglobins Glucosephosphate Dehydrogenase Hydroxyurea
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Nouraie Mehdi
Center for Sickle Cell Disease, Howard University, Washington, DC 20060, USA.
Reading Noel S
Campbell Andrew
Minniti Caterina P
Rana Sohail R
Luchtman-Jones Lori
Kato Gregory J
Gladwin Mark T
Castro Oswaldo L
Prchal Josef T
Gordeuk Victor R
References (37)
37 references, click to expand
  1. Effects of glucose-6-phosphate dehydrogenase deficiency upon sickle cell anemia.
    Blood. 1988 Mar;71(3):748-52 PMID: 3345344
  2. The role of the G6PD AEth376G/968C allele in glucose-6-phosphate dehydrogenase deficiency in the seerer population of Senegal.
    Haematologica. 2006 Feb;91(2):262-3 PMID: 16461316
  3. Relationship of erythropoietin, fetal hemoglobin, and hydroxyurea treatment to tricuspid regurgitation velocity in children with sickle cell disease.
    Blood. 2009 Nov 19;114(21):4639-44 PMID: 19724057
  4. A rapid and reliable 7-deletion multiplex polymerase chain reaction assay for alpha-thalassemia.
    Blood. 2001 Jul 1;98(1):250-1 PMID: 11439976
  5. The effect of fetal hemoglobin on the survival characteristics of sickle cells.
    Blood. 2006 Aug 1;108(3):1073-6 PMID: 16861353
  6. G6PD is indispensable for erythropoiesis after the embryonic-adult hemoglobin switch.
    Blood. 2004 Nov 15;104(10):3148-52 PMID: 15271799
  7. Guidelines and standards for performance of a pediatric echocardiogram: a report from the Task Force of the Pediatric Council of the American Society of Echocardiography.
    J Am Soc Echocardiogr. 2006 Dec;19(12):1413-30 PMID: 17138024
  8. The interaction of alpha-thalassemia and homozygous sickle-cell disease.
    N Engl J Med. 1982 Jun 17;306(24):1441-6 PMID: 6176865
  9. A guide to modern statistical analysis of immunological data.
    BMC Immunol. 2007 Oct 26;8:27 PMID: 17963513
  10. The haematology of steady state homozygous sickle cell disease: interrelationships between haematological indices.
    Br J Haematol. 1987 Aug;66(4):549-58 PMID: 2444245
  11. Evidence that microdeletions in the alpha globin gene protect against the development of sickle cell glomerulopathy in humans.
    J Am Soc Nephrol. 1999 May;10(5):1014-9 PMID: 10232687
  12. Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility.
    Eur J Hum Genet. 2009 Aug;17(8):1080-5 PMID: 19223928
  13. [Hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency in the sub-Saharan immigrant population of the Center and South Maresme region, Catalonia, Spain].
    Med Clin (Barc). 2008 Jun 7;131(1):5-9 PMID: 18582416
  14. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment.
    JAMA. 2003 Apr 2;289(13):1645-51 PMID: 12672732
  15. Fetal haemoglobin in homozygous sickle cell disease.
    Clin Haematol. 1975 Feb;4(1):109-22 PMID: 1102178
  16. alpha-thalassemia in Bantu population from Congo-Brazzaville: its interaction with sickle cell anemia.
    Hum Hered. 2000 Mar-Apr;50(2):118-25 PMID: 10799970
  17. The hemolytic effect of primaquine. IV. The relationship of cell age to hemolysis.
    J Lab Clin Med. 1954 Sep;44(3):439-42 PMID: 13201853
  18. Impact of the method of G6PD deficiency assessment on genetic association studies of malaria susceptibility.
    PLoS One. 2009 Sep 30;4(9):e7246 PMID: 19789650
  19. G6PD deficiency, absence of alpha-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia.
    Blood. 2008 Nov 15;112(10):4314-7 PMID: 18772456
  20. Clinical diversity of sickle cell anemia: genetic and cellular modulation of disease severity.
    Am J Hematol. 1983 Jun;14(4):405-16 PMID: 6190397
  21. Elevated tricuspid regurgitant jet velocity in children and adolescents with sickle cell disease: association with hemolysis and hemoglobin oxygen desaturation.
    Haematologica. 2009 Mar;94(3):340-7 PMID: 19211639
  22. Comparison of homozygous sickle cell disease in northern Greece and Jamaica.
    Lancet. 1990 Mar 17;335(8690):637-40 PMID: 1690325
  23. Induction of hypoxia-inducible factor-1alpha and activation of caspase-3 in hypoxia-reoxygenated bone marrow stroma is negatively regulated by the delayed production of substance P.
    J Immunol. 2001 Oct 15;167(8):4600-8 PMID: 11591789
  24. The percentage of dense red cells does not predict incidence of sickle cell painful crisis.
    Blood. 1986 Jul;68(1):301-3 PMID: 3719102
  25. EFFECT OF AGE ON THE ENZYME ACTIVITY IN ERYTHROCYTES.
    Proc Natl Acad Sci U S A. 1958 Jun;44(6):529-36 PMID: 16590234
  26. Glucose-6-phosphate dehydrogenase deficiency and homozygous sickle cell disease in Jamaica.
    Br J Haematol. 1980 May;45(1):73-80 PMID: 7378331
  27. X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria.
    PLoS Med. 2007 Mar;4(3):e66 PMID: 17355169
  28. Glucose 6-phosphate dehydrogenase deficiency and sickle cell anemia: frequency and features of the association in an African community.
    Blood. 1975 Oct;46(4):591-7 PMID: 1174693
  29. Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease.
    Blood. 1995 Jul 15;86(2):776-83 PMID: 7606007
  30. Glucose-6-phosphate dehydrogenase deficiency and homozygous sickle cell disease in Congo.
    Hum Hered. 1998 Jul-Aug;48(4):192-7 PMID: 9694250
  31. Molecular cloning and nucleotide sequence of cDNA for human glucose-6-phosphate dehydrogenase variant A(-).
    Proc Natl Acad Sci U S A. 1988 Jun;85(11):3951-4 PMID: 2836867
  32. Multiplex genotyping by melting analysis of loci-spanning probes: beta-globin as an example.
    Biotechniques. 2007 Feb;42(2):193-7 PMID: 17373484
  33. Erythroid expansion and survival in response to acute anemia stress: the role of EPO receptor, GATA-1, Bcl-xL and caspase-3.
    Cell Biol Int. 2008 Aug;32(8):966-78 PMID: 18485751
  34. Prevalence of glucose-6-phosphate dehydrogenase deficiency and haemoglobin S in high and moderate malaria transmission areas of Muheza, north-eastern Tanzania.
    Tanzan J Health Res. 2008 Jan;10(1):9-13 PMID: 18680959
  35. UGT1A1 polymorphism outweighs the modest effect of deletional (-3.7 kb) alpha-thalassemia on cholelithogenesis in sickle cell anemia.
    Am J Hematol. 2006 May;81(5):377-9 PMID: 16628735
  36. Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia.
    N Engl J Med. 1982 Feb 4;306(5):270-4 PMID: 6172710
  37. Chronic hyper-hemolysis in sickle cell anemia: association of vascular complications and mortality with less frequent vasoocclusive pain.
    PLoS One. 2008 May 07;3(5):e2095 PMID: 18461136
Article Info
Journal
British journal of haematology
Abbr.
Br J Haematol
ISSN
1365-2141
DOI
10.1111/j.1365-2141.2010.08215.x
Published
2010-07-00
Epub
2010-00-09
Pages
218-25
Language
English
Region
England
NLM ID
0372544
PMCID
PMC2906678
Subset
IM
Grants
Intramural NIH HHS · Z01 CL008098-02 · United States
Intramural NIH HHS · ZIA HL006016-01 · United States
NHLBI NIH HHS · 1 R01 HL079912-02 · United States
NHLBI NIH HHS · R01 HL079912-04 · United States
NHLBI NIH HHS · UH1 HL003679-02 · United States
NCRR NIH HHS · M01 RR010284 · United States
NHLBI NIH HHS · U54 HL090508-02S1 · United States
Intramural NIH HHS · Z01 CL008098-01 · United States
NHLBI NIH HHS · R25 HL003679-08 · United States
NCRR NIH HHS · 2MOI RR10284-10 · United States
NHLBI NIH HHS · 2 R25 HL003679-08 · United States
Intramural NIH HHS · ZIA HL006016-02 · United States
NHLBI NIH HHS · R25 HL003679 · United States
NHLBI NIH HHS · R01 HL079912 · United States
NHLBI NIH HHS · U54 HL090508 · United States
NCRR NIH HHS · M01 RR010284-125835 · United States
External Links
PubMed source DOI: 10.1111/j.1365-2141.2010.08215.x PMC Full Text View journal details
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