Depression and Catechol-O-methyltransferase (COMT) genetic variants are associated with pain in Parkinson\u2019s disease

Chin-Hsien Lin,Alexandra Rizos,Yih-Ru Wu,Han-I. Lin,K. Ray Chaudhuri,Chia-I. Ko,Jun-Yu Fan,Chia-Wen Chang

doi:10.1038/s41598-017-06782-z

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.

Highlights

Grouped COMT function into three haploblocks based on pain response, which covered about 96% of the people tested[15]
Because haplotypes formed by rs6269, rs4633, rs4818, and rs4680 of COMT gene constituted central COMT locus haploblock that is associated with pain response, COMT haplotypes were analyzed in the multivariate regression model to examine the independent effects of various clinical and genetic risk factors contributing to pain in patients with Parkinson disease (PD)
Because haplotypes formed by rs6269, rs4633, rs4818, and rs4680 of COMT gene constituted central COMT locus haploblock that is associated with pain response[15], we examined whether combinations of alleles that were formed by the aforementioned four SNPs of COMT affect the susceptibility to pain in patients with PD

Summary

Introduction

Grouped COMT function into three haploblocks based on pain response, which covered about 96% of the people tested[15]. The examination of the role of COMT polymorphisms and haplotypes with pain perception and severity is of considerable importance in patients with PD. In this study, we explored the contribution of SNPs of nociception-related genes, including COMT and the μ-opioid receptor (OPRM1) and sodium channel Nav1.7 (SCN9A), to the risk and severity of pain in PD. Because haplotypes formed by rs6269, rs4633, rs4818, and rs4680 of COMT gene constituted central COMT locus haploblock that is associated with pain response, COMT haplotypes were analyzed in the multivariate regression model to examine the independent effects of various clinical and genetic risk factors contributing to pain in patients with PD

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