Association of G6PD202A,376G with lower haemoglobin concentration but not increased haemolysis in patients with sickle cell anaemia

Mehdi Nouraie, Noel S. Reading, Andrew Campbell, Caterina P. Minniti, Sohail R. Rana, Lori Luchtman-Jones, Gregory J. Kato, Mark T. Gladwin, Oswaldo L. Castro, Josef T. Prchal, Victor R. Gordeuk

Research output: Contribution to journalArticle

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 G6PD202A and G6PD 376G alleles and α-thalassaemia were determined by molecular genetic testing in 261 children and adolescents with Hb SS in a multicentre study. G6PD202A,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 G6PD202A,376G was 13·6% in males and 3·3% in females with an overall prevalence of 8·7%. G6PD202A,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 α-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, G6PD202A,376G may be associated with lower haemoglobin concentration in sickle cell anaemia by a mechanism other than increased haemolysis.

Original languageEnglish (US)
Pages (from-to)218-225
Number of pages8
JournalBritish Journal of Haematology
Volume150
Issue number2
DOIs
StatePublished - Jul 2010
Externally publishedYes

Fingerprint

Sickle Cell Anemia
Hemolysis
Hemoglobins
Alleles
Reticulocyte Count
Glucosephosphate Dehydrogenase Deficiency
Thalassemia
Globins
Genetic Testing
Aspartate Aminotransferases
L-Lactate Dehydrogenase
Bilirubin
Multicenter Studies
Anemia
Molecular Biology
Pain
hemoglobin P

Keywords

  • alpha-thalassaemia
  • G6PD
  • haemoglobin concentration
  • haemolysis
  • sickle cell anaemia

ASJC Scopus subject areas

  • Hematology

Cite this

Nouraie, M., Reading, N. S., Campbell, A., Minniti, C. P., Rana, S. R., Luchtman-Jones, L., ... Gordeuk, V. R. (2010). Association of G6PD202A,376G with lower haemoglobin concentration but not increased haemolysis in patients with sickle cell anaemia. British Journal of Haematology, 150(2), 218-225. https://doi.org/10.1111/j.1365-2141.2010.08215.x

Association of G6PD202A,376G with lower haemoglobin concentration but not increased haemolysis in patients with sickle cell anaemia. / Nouraie, Mehdi; 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.

In: British Journal of Haematology, Vol. 150, No. 2, 07.2010, p. 218-225.

Research output: Contribution to journalArticle

Nouraie, M, Reading, NS, Campbell, A, Minniti, CP, Rana, SR, Luchtman-Jones, L, Kato, GJ, Gladwin, MT, Castro, OL, Prchal, JT & Gordeuk, VR 2010, 'Association of G6PD202A,376G with lower haemoglobin concentration but not increased haemolysis in patients with sickle cell anaemia', British Journal of Haematology, vol. 150, no. 2, pp. 218-225. https://doi.org/10.1111/j.1365-2141.2010.08215.x
Nouraie, Mehdi ; 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. / Association of G6PD202A,376G with lower haemoglobin concentration but not increased haemolysis in patients with sickle cell anaemia. In: British Journal of Haematology. 2010 ; Vol. 150, No. 2. pp. 218-225.
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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 G6PD202A and G6PD 376G alleles and α-thalassaemia were determined by molecular genetic testing in 261 children and adolescents with Hb SS in a multicentre study. G6PD202A,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 G6PD202A,376G was 13·6{\%} in males and 3·3{\%} in females with an overall prevalence of 8·7{\%}. G6PD202A,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 α-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, G6PD202A,376G may be associated with lower haemoglobin concentration in sickle cell anaemia by a mechanism other than increased haemolysis.",
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