Serum soluble transferrin receptor concentrations are elevated in Congolese children with glucose-6-phosphate dehydrogenase variants, but not sickle cell variants or α-thalassemia

Mikaela K. Barker, Amanda M. Henderson, Karimah Naguib, Suzanne M. Vercauteren, Angela M. Devlin, Arianne Y. Albert, Esto Bahizire, Pierrot L. Tugirimana, Pierre Z. Akilimali, Erick Boy, Tim J. Green, Crystal D. Karakochuk

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. G6PD A- deficiency is characterized by the co-inheritance of G6PD 376 and 202 variants and is common in sub-Saharan Africa. Objective: We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children. Methods: Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect G6PD variants and a-thalassemia deletions. Results: Overall, 11% of children had a sickle cell variant, 19% of boys were G6PD A- hemizygotes, 12% and 10% of girls were G6PD A- hetero- or homozygotes, respectively, and 12% of children had a-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that G6PD A- hemizygous boys and G6PD 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no G6PD variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes. Conclusions: We found that 2 G6PD variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population.

LanguageEnglish
Pages1785-1794
Number of pages10
JournalJournal of Nutrition
Volume147
Issue number9
DOIs
Publication statusPublished - 1 Sep 2017

Keywords

  • Anemia
  • Biomarkers
  • Congo
  • Ferritin
  • Glucose-6-phosphate dehydrogenase
  • Hemoglobinopathy
  • Inflammation
  • Iron
  • Malaria
  • Variant

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Barker, Mikaela K. ; Henderson, Amanda M. ; Naguib, Karimah ; Vercauteren, Suzanne M. ; Devlin, Angela M. ; Albert, Arianne Y. ; Bahizire, Esto ; Tugirimana, Pierrot L. ; Akilimali, Pierre Z. ; Boy, Erick ; Green, Tim J. ; Karakochuk, Crystal D. / Serum soluble transferrin receptor concentrations are elevated in Congolese children with glucose-6-phosphate dehydrogenase variants, but not sickle cell variants or α-thalassemia. In: Journal of Nutrition. 2017 ; Vol. 147, No. 9. pp. 1785-1794.
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title = "Serum soluble transferrin receptor concentrations are elevated in Congolese children with glucose-6-phosphate dehydrogenase variants, but not sickle cell variants or α-thalassemia",
abstract = "Background: Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. G6PD A- deficiency is characterized by the co-inheritance of G6PD 376 and 202 variants and is common in sub-Saharan Africa. Objective: We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children. Methods: Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect G6PD variants and a-thalassemia deletions. Results: Overall, 11{\%} of children had a sickle cell variant, 19{\%} of boys were G6PD A- hemizygotes, 12{\%} and 10{\%} of girls were G6PD A- hetero- or homozygotes, respectively, and 12{\%} of children had a-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that G6PD A- hemizygous boys and G6PD 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95{\%} CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no G6PD variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes. Conclusions: We found that 2 G6PD variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population.",
keywords = "Anemia, Biomarkers, Congo, Ferritin, Glucose-6-phosphate dehydrogenase, Hemoglobinopathy, Inflammation, Iron, Malaria, Variant",
author = "Barker, {Mikaela K.} and Henderson, {Amanda M.} and Karimah Naguib and Vercauteren, {Suzanne M.} and Devlin, {Angela M.} and Albert, {Arianne Y.} and Esto Bahizire and Tugirimana, {Pierrot L.} and Akilimali, {Pierre Z.} and Erick Boy and Green, {Tim J.} and Karakochuk, {Crystal D.}",
year = "2017",
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doi = "10.3945/jn.117.252635",
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pages = "1785--1794",
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Barker, MK, Henderson, AM, Naguib, K, Vercauteren, SM, Devlin, AM, Albert, AY, Bahizire, E, Tugirimana, PL, Akilimali, PZ, Boy, E, Green, TJ & Karakochuk, CD 2017, 'Serum soluble transferrin receptor concentrations are elevated in Congolese children with glucose-6-phosphate dehydrogenase variants, but not sickle cell variants or α-thalassemia', Journal of Nutrition, vol. 147, no. 9, pp. 1785-1794. https://doi.org/10.3945/jn.117.252635

Serum soluble transferrin receptor concentrations are elevated in Congolese children with glucose-6-phosphate dehydrogenase variants, but not sickle cell variants or α-thalassemia. / Barker, Mikaela K.; Henderson, Amanda M.; Naguib, Karimah; Vercauteren, Suzanne M.; Devlin, Angela M.; Albert, Arianne Y.; Bahizire, Esto; Tugirimana, Pierrot L.; Akilimali, Pierre Z.; Boy, Erick; Green, Tim J.; Karakochuk, Crystal D.

In: Journal of Nutrition, Vol. 147, No. 9, 01.09.2017, p. 1785-1794.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Serum soluble transferrin receptor concentrations are elevated in Congolese children with glucose-6-phosphate dehydrogenase variants, but not sickle cell variants or α-thalassemia

AU - Barker, Mikaela K.

AU - Henderson, Amanda M.

AU - Naguib, Karimah

AU - Vercauteren, Suzanne M.

AU - Devlin, Angela M.

AU - Albert, Arianne Y.

AU - Bahizire, Esto

AU - Tugirimana, Pierrot L.

AU - Akilimali, Pierre Z.

AU - Boy, Erick

AU - Green, Tim J.

AU - Karakochuk, Crystal D.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Background: Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. G6PD A- deficiency is characterized by the co-inheritance of G6PD 376 and 202 variants and is common in sub-Saharan Africa. Objective: We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children. Methods: Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect G6PD variants and a-thalassemia deletions. Results: Overall, 11% of children had a sickle cell variant, 19% of boys were G6PD A- hemizygotes, 12% and 10% of girls were G6PD A- hetero- or homozygotes, respectively, and 12% of children had a-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that G6PD A- hemizygous boys and G6PD 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no G6PD variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes. Conclusions: We found that 2 G6PD variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population.

AB - Background: Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. G6PD A- deficiency is characterized by the co-inheritance of G6PD 376 and 202 variants and is common in sub-Saharan Africa. Objective: We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children. Methods: Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect G6PD variants and a-thalassemia deletions. Results: Overall, 11% of children had a sickle cell variant, 19% of boys were G6PD A- hemizygotes, 12% and 10% of girls were G6PD A- hetero- or homozygotes, respectively, and 12% of children had a-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that G6PD A- hemizygous boys and G6PD 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no G6PD variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes. Conclusions: We found that 2 G6PD variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population.

KW - Anemia

KW - Biomarkers

KW - Congo

KW - Ferritin

KW - Glucose-6-phosphate dehydrogenase

KW - Hemoglobinopathy

KW - Inflammation

KW - Iron

KW - Malaria

KW - Variant

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U2 - 10.3945/jn.117.252635

DO - 10.3945/jn.117.252635

M3 - Article

VL - 147

SP - 1785

EP - 1794

JO - Journal of Nutrition

T2 - Journal of Nutrition

JF - Journal of Nutrition

SN - 0022-3166

IS - 9

ER -