ArticleAmerican journal of hematology2014
A GCH1 haplotype confers sex-specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia.
Article in American journal of hematology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.Pain reports · 2021Trial
- Modeling Pain Without Injury: Inherited Rodent Models as Mechanistic Windows into Chronic Pain.Function (Oxford, England) · 2025Review
- Genetic Modifiers Associated with Vaso-Occlusive Crises and Acute Pain Phenomena in Sickle Cell Disease: A Scoping Review.International journal of molecular sciences · 2025Article
- From a clinically relevant pain target to a possible analgesic treatment strategy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Genetic contributions to pain modulation in sickle cell: A focus on single nucleotide polymorphisms.Gene reports · 2024Article
- Can we use biomarkers to identify those at risk of acute pain from sickle cell disease?Expert review of hematology · 2024Review
- In Silico Investigation of the Human GTP Cyclohydrolase 1 Enzyme Reveals the Potential of Drug Repurposing Approaches towards the Discovery of Effective BHInternational journal of molecular sciences · 2023Article
- Differential clinical characteristics across traditional Chinese medicine (TCM) Syndromes in patients with sickle cell disease.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Single nucleotide polymorphisms and sickle cell disease-related pain: a systematic review.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy.Frontiers in pharmacology · 2023Review
- Sepiapterin reductase: Characteristics and role in diseases.Journal of cellular and molecular medicine · 2020Review
- Qualitative sex differences in pain processing: emerging evidence of a biased literature.Nature reviews. Neuroscience · 2020Review
- Article
- GCH1 haplotypes and cardiovascular risk in HIV.AIDS (London, England) · 2019Article
- Article
- Sickle cell disease in the era of precision medicine: looking to the future.Expert review of precision medicine and drug development · 2019Article
- Genetic variants of GCH1 associate with chronic and acute crisis pain in African Americans with sickle cell disease.Experimental hematology · 2018Article
- Glucocorticoid receptor single nucleotide polymorphisms are associated with acute crisis pain in sickle cell disease.Pharmacogenomics · 2018Article
- Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer's disease pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
Abstract
GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21-5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.