title: Lack of genetic association of neutral endopeptidase (NEP) with complex regional pain syndrome (CRPS).
abstract: Complex regional pain syndrome (CRPS) is a condition that is characterized by severe pain and exaggerated neurogenic inflammation, which may develop after injury or surgery. Neurogenic inflammation is mediated by neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P (SP) that are released from nociceptors. Genetic factors may play a role in CRPS as was suggested by the occurrence of familial cases and several genetic association studies investigating mainly the human leukocyte antigen (HLA) system. Here we investigated the role of neutral endopeptidase (NEP), a key enzyme in neuropeptide catabolism. NEP dysfunction resulting in reduced inactivation of neuropeptides may be a possible pathomechanism in CRPS. To this end, we tested a GT-repeat polymorphism in the NEP promoter region as well as 18 tag-SNPs in six linkage disequilibrium (LD) blocks in the NEP gene region in 320 CRPS patients and 376 controls. No significant genetic association was observed. Thus, we conclude that the NEP gene does not seem to be a major risk factor for CRPS.
authors.affiliation: Institute of Human Genetics, University Hospital Erlangen-Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany. Kathrin.Huehne@uk-erlangen.de
authors.forename: Kathrin
authors.initials: K
authors.lastname: Huehne
authors.forename: Ute
authors.initials: U
authors.lastname: Schaal
authors.forename: Stefan
authors.initials: S
authors.lastname: Leis
authors.forename: Steffen
authors.initials: S
authors.lastname: Uebe
authors.forename: M Florencia
authors.initials: MF
authors.lastname: Gosso
authors.forename: Arn M J M
authors.initials: AM
authors.lastname: van den Maagdenberg
authors.forename: Christian
authors.initials: C
authors.lastname: Maihöfner
authors.forename: Frank
authors.initials: F
authors.lastname: Birklein
authors.forename: Bernd
authors.initials: B
authors.lastname: Rautenstrauss
authors.forename: Andreas
authors.initials: A
authors.lastname: Winterpacht
mesh_terms: D024506:5' Flanking Region; D000328:Adult; D016022:Case-Control Studies; D020918:Complex Regional Pain Syndromes / Q000235:genetics*; D018900:Dinucleotide Repeats; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D015260:Neprilysin