Rodolphe Maheux Award 2023 presented to Scott MacKenzie

30 November 2023

The 2023 Rodolphe Maheux Award for best Clinical Abstract was presented to Scott MacKenzie at the closing ceremony of the 15th World Congress on Endometriosis for his work on how Genome-wide association reveals a locus in Neuregulin 3 associated with gabapentin efficacy in women with chronic pelvic pain.

MacKenzie S1, Rahmioglu N2,3, Collins F1, Coxon L3, Vincent K3, Zondervan K2,3, Horne A1, Whitaker L1
1MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom, 2Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, 3Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United Kingdom

Chronic pelvic pain (CPP) in women with no obvious pelvic pathology has few evidence-based treatment options. Our recent multicentre randomised controlled trial (GaPP2) in women with CPP showed that gabapentin did not relieve pain and was associated with higher rates of side-effects than placebo. However, the data suggest that subgroups of women could benefit from gabapentin.

To identify if common genetic variants are associated with gabapentin response in women with CPP with no obvious pelvic pathology.

Materials and Methods:
We conducted a genome-wide association study of gabapentin response, using participants from GaPP2. Two phenotypes were investigated: gabapentin analgesic response (≥30% reduction in worst and/or average pain), and side-effect burden (≥3 side-effects reported). Standard genetic quality control was conducted followed by imputation to HRC reference panel. Frequentist association analysis was conducted
in SNPTEST including autosomes and chromosome X.

93 participants provided salivary samples for genotyping (82 passed quality control) and 5,522,729 SNPs were tested for association (n=29 ≥30% vs. n=42 <30% reduction in worst and/or average pain scores). One genome-wide significant association with gabapentin analgesic response was identified, rs4442490, an intron variant located in Neuregulin 3 (NRG3) at 10q23.1 (p=2.11×10−8; OR=18.82 (95%CI 4.86–72.83);
MAF=0.42). NRG3 is expressed predominantly in brain tissues and involved in nervous system maintenance/repair. No SNPs reached genome-wide significance for gabapentin side-effect burden.

Conclusion and impact:
A locus in NRG3 is associated with gabapentin efficacy in women with CPP with no obvious pelvic pathology, highlighting the possibility of a precision medicine approach to symptom management.