Contribution of genetic variants to pain susceptibility in Parkinson disease.

Abstract

BACKGROUND:

Pain is a one of the most disturbing non-motor symptoms of Parkinson disease (PD). The susceptibility to pain varies substantially among patients with PD. The aim of this study was to assess a potential association of genetic variants to PD-related pain.

METHODS:

We analysed 20 candidate SNPs from 12 genes previously reported to be associated with various pain phenotypes in a homogeneous group of 229 Israeli Jewish PD patients, with and without pain (n = 165 and 64, respectively).

RESULTS:

The statistical analysis accounted for the potential influence of demographic and clinical factors. The non-synonymous rs6746030 single nucleotide polymorphism (SNP) of the SCN9A gene, which alters the coding sequence of the sodium channel Nav1.7 (arginine to tryptophan), was nominally associated with PD-related pain susceptibility (p = 0.037), as well as with central and musculoskeletal pain subtypes independently. The synonymous rs324419 SNP of the FAAH gene which encodes fatty acid amide hydrolase, a cannabinoid metabolizing enzyme, was associated with PD-related pain (p = 0.006) and specifically with the musculoskeletal subtype. The FAAH haplotype of rs324419 and rs2295633 SNPs, which was previously associated with the variability in pain response in humans, was also associated with PD-related pain (p = 0.012) and specifically with PD-related musculoskeletal pain.

CONCLUSIONS:

Variants within in the SCN9A and FAAH genes were associated with the risk of pain in PD patients. These findings may contribute to our understanding of pain mechanisms of PD and to direct future therapies.

• Authors: L Greenbaum, I Tegeder, Y Barhum, E Melamed, Y Roditi, R Djaldetti
• Journal: European journal of pain (London, England) (Eur J Pain) Vol. 16 Issue 9 Pg. 1243-50 (Oct 2012) ISSN: 1532-2149 [Electronic] England
• PMID: 22473870 (Publication Type: Journal Article)
• Copyright: © 2012 European Federation of International Association for the Study of Pain Chapters.

Chemical References

• Brain-Derived Neurotrophic Factor
• CACNG2 protein, human
• Calcium Channels
• Interleukin-1alpha
• Interleukin-1beta
• NAV1.7 Voltage-Gated Sodium Channel
• OPRD1 protein, human
• OPRM1 protein, human
• Receptor, Melanocortin, Type 1
• Receptors, Opioid, delta
• Receptors, Opioid, mu
• SCN9A protein, human
• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins
• TRPV Cation Channels
• TRPV1 protein, human
• Catechol O-Methyltransferase
• Amidohydrolases
• fatty-acid amide hydrolase

Topics

• Aged
• Amidohydrolases (genetics)
• Brain-Derived Neurotrophic Factor (genetics)
• Calcium Channels (genetics)
• Catechol O-Methyltransferase (genetics)
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• Interleukin-1alpha (genetics)
• Interleukin-1beta (genetics)
• Jews (genetics)
• Male
• Middle Aged
• NAV1.7 Voltage-Gated Sodium Channel (genetics)
• Pain (etiology, genetics)
• Parkinson Disease (complications, genetics)
• Phenotype
• Polymorphism, Single Nucleotide
• Receptor, Melanocortin, Type 1 (genetics)
• Receptors, Opioid, delta (genetics)
• Receptors, Opioid, mu (genetics)
• Serotonin Plasma Membrane Transport Proteins (genetics)
• TRPV Cation Channels (genetics)