Palliative Medicine in Practice · Published 2026-01-30 · DOI 10.5603/pmp.110189
BACKGROUND: There are considerable inter-individual differences in the symptomatic response to morphine in people with chronic breathlessness, some of which may be explained by genetic variations. Is there any association between candidate single nucleotide polymorphisms (SNPs) in opioid pathways and breathlessness when morphine or placebo is initiated in people with chronic breathlessness? METHODS: Participants (n = 136) were included from two multi-site, randomised, placebo-controlled trials of regular, low-dose, sustained-release morphine for chronic breathlessness. All were genotyped for COMT rs4680 and rs4818, HTR3B rs7103572 and OPRM1 rs1799971. “Worst,” “average” and “unpleasantness” of breathlessness are reported from baseline and the mean of days 5–7 on a 0–100 mm visual analogue scale. Genotype differences at baseline and changes in breathlessness were explored using linear regression. RESULTS: Baseline “average” breathlessness was significantly higher in HTR3B rs7103572 C/T (mean ± SD = 52 ± 15 mm) versus C/C (44 ± 16 mm; p = 0.02), and COMT rs4680 G/G (55 ± 19 mm) versus A/A (44 ± 16 mm; p = 0.04). Reductions in breathlessness were significantly greater (post-hoc p < 0.05) in HTR3B rs7103572 T/T versus C/T and C/C, respectively, for: (1) worst [median (IQR) change = −28 (−44, −19), –5 (−20, 5), −10 (−20, 6) mm]; (2) average [–20 (–42, –8), –6 (–19, 7), –2 (–13, 8) mm]; and (3) unpleasantness [–32 (–43, –10), –7 (–20, 3), –1 (–17, 5) mm]. There were no differences between the morphine and placebo arms for response. CONCLUSIONS: HTRB3 and COMT genotypes may influence baseline measures of chronic breathlessness, whilst HTRB3 genotype may additionally affect symptomatic response to morphine and placebo. These findings begin to create a foundation for personalised medicine in chronic breathlessness.
Abstract from DOAJ. Public domain (CC0 1.0).
Read the article at the publisher →