New cases of glucose-6-phosphate dehydrogenase deficiency in pulmonary arterial hypertension

Sergey Kurdyukov, Cody A. Eccles, Ankit Desai, Manuel Gonzalez-Garay, Jason Yuan, Joe GN Garcia, Olga Rafikova, Ruslan Rafikov

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Pulmonary Arterial Hypertension (PAH) is a fatal disorder with limited treatment options and reduced life expectancy after diagnosis. Complex genetic backgrounds in PAH complicates identification of causative mutations that is essential for an understanding of the disease diagnostics and etiology especially for idiopathic PAH (iPAH). Hemolysis has been implicated as contributing to the pathobiology of PAH. Glucose-6-Phosphate Dehydrogenase (G6PD) expression and activity define erythrocyte’s antioxidant capacity, and its decrease contributes to erythrocyte fragility. As G6PD deficiency was previously reported in a limited number of PAH cases, we tested whether iPAH patients exhibit underlying G6PD alterations in erythrocytes. A cohort of 22 PAH patients and 8 non-PAH patients were recruited for this study. DNA isolated from Peripheral Blood Mononuclear Cells (PBMC) was used for detection of mutations in the coding region of the G6PD gene. RNA isolated from PBMC was used for determination of G6PD mRNA expression level. G6PD activity was measured in Red Blood Cell (RBC) pellets. Three patients had missense mutations in G6PD (Val291Met, Asn126Asp, Asp194Glu), however, only one mutation (Val291Met) results in a severe G6PD deficiency. A single patient with mutation (Asn126Asp) showed a 21% decrease in G6PD activity, two subjects showed G6PD deficiency without mutations, and one patient had a decreased level of G6PD mRNA and reduced enzyme levels. This study demonstrates that a moderate decrease in G6PD activity is associated with PAH. Screening for G6PD activity and mutations in the G6PD gene may provide early detection of individuals predisposed to PAH.

Original languageEnglish (US)
Article numbere0203493
JournalPLoS One
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Glucosephosphate Dehydrogenase Deficiency
Glucosephosphate Dehydrogenase
glucose-6-phosphate 1-dehydrogenase
Pulmonary Hypertension
hypertension
lungs
Mutation
mutation
Erythrocytes
erythrocytes
Blood
Blood Cells
mononuclear leukocytes
Messenger RNA
Genes
Missense Mutation
Life Expectancy
Hemolysis
missense mutation
hemolysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

New cases of glucose-6-phosphate dehydrogenase deficiency in pulmonary arterial hypertension. / Kurdyukov, Sergey; Eccles, Cody A.; Desai, Ankit; Gonzalez-Garay, Manuel; Yuan, Jason; Garcia, Joe GN; Rafikova, Olga; Rafikov, Ruslan.

In: PLoS One, Vol. 13, No. 8, e0203493, 01.08.2018.

Research output: Contribution to journalArticle

Kurdyukov, Sergey ; Eccles, Cody A. ; Desai, Ankit ; Gonzalez-Garay, Manuel ; Yuan, Jason ; Garcia, Joe GN ; Rafikova, Olga ; Rafikov, Ruslan. / New cases of glucose-6-phosphate dehydrogenase deficiency in pulmonary arterial hypertension. In: PLoS One. 2018 ; Vol. 13, No. 8.
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