2024-07-15 エディンバラ大学
<関連情報>
- https://www.ed.ac.uk/news/2024/tell-tale-gene-affects-success-of-pain-drug
- https://www.cell.com/iscience/fulltext/S2589-0042(24)01595-5
慢性骨盤痛女性におけるガバペンチンの有効性に関連するニューレグリン3の遺伝子座がゲノムワイド関連で発見される Genome-wide association reveals a locus in neuregulin 3 associated with gabapentin efficacy in women with chronic pelvic pain
Scott C. Mackenzie,Nilufer Rahmioglu,Liana Romaniuk,…,Krina T. Zondervan,Andrew W. Horne
iScience Published:July 15, 2024
DOI:https://doi.org/10.1016/j.isci.2024.110370
Graphical abstract
Highlights
- Gabapentin response GWAS was performed in a cohort of women with chronic pelvic pain
- A locus in Neuregulin 3 (NRG3) was associated with gabapentin analgesic efficacy
- NRG3 is expressed in nervous system tissues and involved in regulation and repair
- There may be potential for a personalised medicine approach to gabapentin treatment
Summary
Chronic pelvic pain (CPP) in women with no obvious pelvic pathology has few evidence-based treatment options. Our recent multicenter randomized controlled trial (GaPP2) in women with CPP and no obvious pelvic pathology showed that gabapentin did not relieve pain overall and was associated with more side effects than placebo. We conducted an exploratory genome-wide association study using eligible GaPP2 participants aiming to identify genetic variants associated with gabapentin response. One genome-wide significant association with gabapentin analgesic response was identified, rs4442490, an intron variant located in Neuregulin 3 (NRG3) (p = 2·11×10-8; OR = 18·82 (95% CI 4·86–72·83). Analysis of a large sample of UK Biobank participants demonstrated phenome-wide significant brain imaging features of rs4442490, particularly implicating the orbitofrontal cortex. NRG3 is expressed predominantly in central nervous system tissues and plays a critical role in nervous system development, maintenance, and repair, suggesting a neurobiologically plausible role in gabapentin efficacy and potential for personalized analgesic treatment.
