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Contribution of genetic variants to pain susceptibility in P arkinson disease
Author(s) -
Greenbaum L.,
Tegeder I.,
Barhum Y.,
Melamed E.,
Roditi Y.,
Djaldetti R.
Publication year - 2012
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/j.1532-2149.2012.00134.x
Subject(s) - fatty acid amide hydrolase , single nucleotide polymorphism , snp , haplotype , chronic pain , medicine , candidate gene , genetic predisposition , disease , bioinformatics , genetics , gene , biology , genotype , physical therapy , cannabinoid receptor , receptor , agonist
Background Pain is a one of the most disturbing non‐motor symptoms of P arkinson 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 I sraeli J ewish 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 rs 6746030 single nucleotide polymorphism ( SNP ) of the SCN9A gene, which alters the coding sequence of the sodium channel N av1.7 (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 rs 324419 and rs 2295633 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.