Depression and Catechol-O-methyltransferase (COMT) genetic variants are associated with pain in Parkinson’s disease

Abstract

Pain is a distressing symptom of Parkinson disease (PD). We aim to determine whether the genetic variants of chronic pain-related genes contribute to pain in PD patients. We included 418 PD patients and evaluated pain severity on King’s PD pain scale. We genotyped rs6267, rs6269, rs4633, rs4818 and rs4680 of COMT, rs6746030 of SCN9A, and rs1799971 of OPRM1. In total, 193 participants (46.2%) experienced pain. Compared to pain-free PD patients, PD patients with pain had an earlier age of onset, longer disease duration, and higher depression and motor severity (P < 0.01). The frequencies of COMT rs4680 “A” allele were higher in PD patients with pain than those without pain (46.1% vs. 31.1%, P < 0.01). Pain severity was significantly associated with disease duration (P = 0.02), and COMT rs6267 T allele (P < 0.01). We stratified PD by status of depression and the association between COMT rs6267 “GT” genotype and pain severity remained significant (P < 0.01). Furthermore, pain severity was significantly higher in participants having COMT rs4680 “GG” and “GA” genpotypes than those having “AA” genotype (P = 0.04). We concluded that depression and COMT rs4680 “GG” and “GA” genotypes and COMT rs6267 “GT” genotype contribute to pain in PD patients.

Contribution of Five Functional Loci of Dopamine Metabolism-Related Genes to Parkinson’s Disease and Multiple System Atrophy in a Chinese Population

“…The broader role of dopamine in the CNS suggests that other phenotypes could be affected in PD, such as pain (Lin et al, 2017), daytime sleepiness (Rissling et al, 2006), and apathy (Cramer et al, 2010;Hong et al, 2015;Masala et al, 2018), all of which are very frequent symptoms in Parkinson's disease patients as reported in previous studies. Although PD patients harboring COMT rs4680 seemed to have a reduced risk of developing depression, the minor COMT rs4680 and TH rs6356 alleles exerted a protective effect on cognitive function in PD patients, and DBH rs1611115 tended to increase the risk for impaired cognition in PD in the subgroup analysis.…”

Catechol-O-methyltransferase (COMT) genetic variants are associated with cognitive decline in patients with Parkinson's disease

“…Furthermore, haplotypes formed by rs6269, rs4633, rs4818, and rs4680 of the COMT gene constitute a central COMT locus haploblock that is associated with the enzymatic activity of COMT [8]. The SNPs rs6269 and rs4818, which are located in the central COMT locus haploblock, have been observed to be associated with pain sensitivity in patients with chronic pain syndrome [8,19]. Therefore, we focused our analyses on this central haploblock, covering the order of occurrence from 5 0 to 3 0 in the COMT gene as rs6269, rs4633, rs4818, and rs4680 ( Fig.…”

The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial

“…We discovered a significant effect of the COMT-rs4680 polymorphism on the C max , AUC 0-∞ and Cl of ATV, although this effect was not supported by regression analysis. The rs4680 variant produces a non-synonymous amino acid change (p.V158M) causing impaired COMT activity 44,45 . As far as we know this is the first study that reports a possible effect of COMT-rs4680 on ATV pharmacokinetics.…”