Heterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not pain sensitivity

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Standard

Heterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not pain sensitivity. / Nasser, Arafat; Møller, Anette Torvin; Hellmund, Vibe; Thorborg, Sidsel Salling; Jespersgaard, Cathrine; Bjerrum, Ole J.; Dupontd, Erik; Nachman, Gösta; Lykkesfeldt, Jens; Jensen, Troels Staehelin; Møller, Lisbeth Birk.

In: Pain, Vol. 159, No. 6, 2018, p. 1012-1024.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Nasser, A, Møller, AT, Hellmund, V, Thorborg, SS, Jespersgaard, C, Bjerrum, OJ, Dupontd, E, Nachman, G, Lykkesfeldt, J, Jensen, TS & Møller, LB 2018, 'Heterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not pain sensitivity', Pain, vol. 159, no. 6, pp. 1012-1024. https://doi.org/10.1097/j.pain.0000000000001175

APA

Nasser, A., Møller, A. T., Hellmund, V., Thorborg, S. S., Jespersgaard, C., Bjerrum, O. J., ... Møller, L. B. (2018). Heterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not pain sensitivity. Pain, 159(6), 1012-1024. https://doi.org/10.1097/j.pain.0000000000001175

Vancouver

Nasser A, Møller AT, Hellmund V, Thorborg SS, Jespersgaard C, Bjerrum OJ et al. Heterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not pain sensitivity. Pain. 2018;159(6):1012-1024. https://doi.org/10.1097/j.pain.0000000000001175

Author

Nasser, Arafat ; Møller, Anette Torvin ; Hellmund, Vibe ; Thorborg, Sidsel Salling ; Jespersgaard, Cathrine ; Bjerrum, Ole J. ; Dupontd, Erik ; Nachman, Gösta ; Lykkesfeldt, Jens ; Jensen, Troels Staehelin ; Møller, Lisbeth Birk. / Heterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not pain sensitivity. In: Pain. 2018 ; Vol. 159, No. 6. pp. 1012-1024.

Bibtex

@article{ee592f97a1434d4faa42d1df29ca6228,
title = "Heterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not pain sensitivity",
abstract = "Human studies have demonstrated a correlation between noncoding polymorphisms of {"}the pain protective{"} haplotype in the GCH1 gene that encodes for GTP cyclohydrolase I (GTPCH1)-which leads to reduced tetrahydrobiopterin (BH4) production in cell systems-and a diminished perception of experimental and clinical pain. Here, we investigate whether heterozygous mutations in the GCH1 gene which lead to a profound BH4 reduction in patients with dopa-responsive dystonia (DRD) have any effect on pain sensitivity. The study includes an investigation of GCH1-associated biomarkers and pain sensitivity in a cohort of 22 patients with DRD and 36 controls. The patients with DRD had, when compared with controls, significantly reduced levels of BH4, neopterin, biopterin, and GTPCH1 in their urine, blood, or cytokine-stimulated fibroblasts, but their pain response with respect to non-painful stimulation, (acute) stimulus-evoked pain, or pain response after capsaicin-induced sensitization was not significantly different. A family-specific cohort of 11 patients with DRD and 11 controls were included in this study. The patients with DRD were heterozygous for the pain protective haplotype in cis with the GCH1 disease-causing mutation, c.899T.C. No effect on pain perception was observed for this combined haplotype. In conclusion, a reduced concentration of BH4 is not sufficient to alter ongoing pain sensitivity or evoked pain responses.",
keywords = "Capsaicin, DOPA-responsive dystonia, GCH1, GTP cyclohydrolase 1, GTPCH, Pain, Tetrahydrobiopterin",
author = "Arafat Nasser and M{\o}ller, {Anette Torvin} and Vibe Hellmund and Thorborg, {Sidsel Salling} and Cathrine Jespersgaard and Bjerrum, {Ole J.} and Erik Dupontd and G{\"o}sta Nachman and Jens Lykkesfeldt and Jensen, {Troels Staehelin} and M{\o}ller, {Lisbeth Birk}",
year = "2018",
doi = "10.1097/j.pain.0000000000001175",
language = "English",
volume = "159",
pages = "1012--1024",
journal = "Pain",
issn = "0304-3959",
publisher = "IASP Press",
number = "6",

}

RIS

TY - JOUR

T1 - Heterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not pain sensitivity

AU - Nasser, Arafat

AU - Møller, Anette Torvin

AU - Hellmund, Vibe

AU - Thorborg, Sidsel Salling

AU - Jespersgaard, Cathrine

AU - Bjerrum, Ole J.

AU - Dupontd, Erik

AU - Nachman, Gösta

AU - Lykkesfeldt, Jens

AU - Jensen, Troels Staehelin

AU - Møller, Lisbeth Birk

PY - 2018

Y1 - 2018

N2 - Human studies have demonstrated a correlation between noncoding polymorphisms of "the pain protective" haplotype in the GCH1 gene that encodes for GTP cyclohydrolase I (GTPCH1)-which leads to reduced tetrahydrobiopterin (BH4) production in cell systems-and a diminished perception of experimental and clinical pain. Here, we investigate whether heterozygous mutations in the GCH1 gene which lead to a profound BH4 reduction in patients with dopa-responsive dystonia (DRD) have any effect on pain sensitivity. The study includes an investigation of GCH1-associated biomarkers and pain sensitivity in a cohort of 22 patients with DRD and 36 controls. The patients with DRD had, when compared with controls, significantly reduced levels of BH4, neopterin, biopterin, and GTPCH1 in their urine, blood, or cytokine-stimulated fibroblasts, but their pain response with respect to non-painful stimulation, (acute) stimulus-evoked pain, or pain response after capsaicin-induced sensitization was not significantly different. A family-specific cohort of 11 patients with DRD and 11 controls were included in this study. The patients with DRD were heterozygous for the pain protective haplotype in cis with the GCH1 disease-causing mutation, c.899T.C. No effect on pain perception was observed for this combined haplotype. In conclusion, a reduced concentration of BH4 is not sufficient to alter ongoing pain sensitivity or evoked pain responses.

AB - Human studies have demonstrated a correlation between noncoding polymorphisms of "the pain protective" haplotype in the GCH1 gene that encodes for GTP cyclohydrolase I (GTPCH1)-which leads to reduced tetrahydrobiopterin (BH4) production in cell systems-and a diminished perception of experimental and clinical pain. Here, we investigate whether heterozygous mutations in the GCH1 gene which lead to a profound BH4 reduction in patients with dopa-responsive dystonia (DRD) have any effect on pain sensitivity. The study includes an investigation of GCH1-associated biomarkers and pain sensitivity in a cohort of 22 patients with DRD and 36 controls. The patients with DRD had, when compared with controls, significantly reduced levels of BH4, neopterin, biopterin, and GTPCH1 in their urine, blood, or cytokine-stimulated fibroblasts, but their pain response with respect to non-painful stimulation, (acute) stimulus-evoked pain, or pain response after capsaicin-induced sensitization was not significantly different. A family-specific cohort of 11 patients with DRD and 11 controls were included in this study. The patients with DRD were heterozygous for the pain protective haplotype in cis with the GCH1 disease-causing mutation, c.899T.C. No effect on pain perception was observed for this combined haplotype. In conclusion, a reduced concentration of BH4 is not sufficient to alter ongoing pain sensitivity or evoked pain responses.

KW - Capsaicin

KW - DOPA-responsive dystonia

KW - GCH1

KW - GTP cyclohydrolase 1

KW - GTPCH

KW - Pain

KW - Tetrahydrobiopterin

U2 - 10.1097/j.pain.0000000000001175

DO - 10.1097/j.pain.0000000000001175

M3 - Journal article

VL - 159

SP - 1012

EP - 1024

JO - Pain

JF - Pain

SN - 0304-3959

IS - 6

ER -

ID: 202033947