Genetic variation in catechol-O-methyltransferase is associated with individual differences in conditioned pain modulation in healthy subjects
| Autor: | Eli Eliav, Cibele Nasri-Heir, Fengshen Kuo, Scott R. Diehl, Ching-Yu Huang, Rafael Benoliel, Craig Hirschberg, Olga A. Korczeniewska, Junad Khan |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Pain Threshold medicine.medical_specialty Genotype DNA Mutational Analysis Individuality Pain Single-nucleotide polymorphism Biology Catechol O-Methyltransferase Polymorphism Single Nucleotide Article Young Adult Internal medicine Drug Discovery Genetic variation Genetics medicine SNP Humans Molecular Biology Genetics (clinical) Genetic Association Studies Aged Pain Measurement Aged 80 and over Catechol-O-methyl transferase Haplotype Chronic pain Middle Aged medicine.disease Healthy Volunteers Endocrinology Haplotypes Molecular Medicine Female rs4680 |
| Zdroj: | J Gene Med |
| ISSN: | 1521-2254 |
| Popis: | BACKGROUND: Genetic variation in the catechol-O-methyltransferase (COMT) gene is associated with sensitivity to both acute experimental pain and chronic pain conditions. Four single nucleotide polymorphisms (SNPs) have traditionally been used to infer three common haplotypes designated as low, average and high pain sensitivity and are reported to affect both COMT enzymatic activity and pain sensitivity. One mechanism that may partly explain individual differences in sensitivity to pain is conditioned pain modulation (CPM). We hypothesized that variation in CPM may have a genetic basis. METHODS: We evaluated CPM in 77 healthy pain-free Caucasian subjects by applying repeated mechanical stimuli to the dominant forearm using 26-g von Frey filament as the test stimulus with immersion of the non-dominant hand in hot water as the conditioning stimulus. We assayed COMT SNP genotypes by the TaqMan method using DNA extracted from saliva. RESULTS: SNP rs4680 (val(158)met) was not associated with individual differences in CPM. However, CPM was associated with COMT low pain sensitivity haplotypes under an additive model (p = 0.004) and the effect was independent of gender. CONCLUSIONS: We show that, although four SNPs are used to infer COMT haplotypes, the low pain sensitivity haplotype is determined by SNP rs6269 (located in the 5′ regulatory region of COMT), suggesting that inherited variation in gene expression may underlie individual differences in pain modulation. Analysis of 13 global populations revealed that the COMT low pain sensitivity haplotype varies in frequency from 13% to 44% and showed that two SNPs are sufficient to distinguish all COMT haplotypes in most populations. |
| Databáze: | OpenAIRE |
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