Neanderthal introgression in SCN9A impacts mechanical pain sensitivity.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
10 10 2023
10 10 2023
Historique:
received:
24
02
2023
accepted:
25
08
2023
medline:
1
11
2023
pubmed:
11
10
2023
entrez:
10
10
2023
Statut:
epublish
Résumé
The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of ~123 kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function.
Identifiants
pubmed: 37816865
doi: 10.1038/s42003-023-05286-z
pii: 10.1038/s42003-023-05286-z
pmc: PMC10564861
doi:
Substances chimiques
NAV1.7 Voltage-Gated Sodium Channel
0
SCN9A protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
958Subventions
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 223149/Z/21/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 222101/Z/20/Z
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Versus Arthritis
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/I021213/1
Pays : United Kingdom
Informations de copyright
© 2023. Springer Nature Limited.
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