rs2183080

This variant is located in the GCH1 gene.

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GWAS Catalog Trait Associations (1)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

3-methoxytyrosine measurement

Hysi PG et al. “Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels.” Metabolites 12(1) (2022)

Allele C

OR 0.23

p 2.0e-23

N 8,809

Large GWAS

European

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ClinVar annotation

Benign★★★☆

2 submitters1 publication

View on ClinVar →

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Research that mentions this SNP (1)

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The COMT rs4680 Met allele contributes to long‐lasting low back pain, sciatica and disability after lumbar disc herniation

ReviewJacobsen LM et al.(2012)· European Journal of Pain

This review examines polymorphisms in six genes (SCN9A, KCNS1, GCH1, COMT, OPRM1, OPRK1) involved in nociception and their associations with chronic post-surgical pain (CPSP). Key findings include rs4680 in COMT associated with higher pain risk (OR 3.42 in knee replacement patients), rs734784 in KCNS1 explaining ~5% of pain variance in lumbar discectomy patients, and rs6746030 in SCN9A conferring increased pain sensitivity. The paper reviews conflicting evidence across multiple surgical populations and discusses potential clinical applications of genetic testing for CPSP risk stratification.

Traits studied:Chronic post-surgical pain (CPSP)Neuropathic painOpioid responsePain intensityPain sensitivityPostoperative pain

PubMed DOI Metascience Observatory

About GCH1

This gene encodes a member of the GTP cyclohydrolase family. The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an essential cofactor required by aromatic amino acid hydroxylases as well as nitric oxide synthases. Mutations in this gene are associated with malignant hyperphenylalaninemia and dopa-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all variants give rise to a functional enzyme. [provided by RefSeq, Jul 2008]