Association Between CTSG Variants and Persistent Postoperative Pain After Cardiac Surgery

Area of Science:

• Genetics and Molecular Biology
• Pain Research
• Cardiovascular Surgery

Background:

• Cathepsin G (CTSG), a neutrophil protease, plays a role in inflammatory pain.
• Genetic variations in CTSG may affect susceptibility to postoperative pain.
• Understanding CTSG's role is crucial for managing long-term pain after cardiac surgery.

Purpose of the Study:

• To investigate the association between CTSG gene polymorphisms, plasma concentration, enzymatic activity, and long-term pain after cardiac surgery.
• To evaluate the influence of specific CTSG single nucleotide polymorphisms (SNPs) on pain outcomes.
• To explore potential mechanisms linking CTSG to persistent postoperative pain.

Main Methods:

• Prospective cohort study of 255 Caucasian adults undergoing elective cardiac surgery.
• Genotyping of CTSG SNPs (rs2070697, rs2236742, rs45567233) and measurement of CTSG plasma concentration and activity in a subsample.
• Assessment of pain intensity using visual analogue scale (VAS) at multiple time points (24 hours, 1, 6, 12 months).
• Statistical analysis using ordinal logistic regression and Mendelian randomization.

Main Results:

• The rs2070697 AA genotype was linked to reduced pain at 1, 6, and 12 months post-surgery.
• The rs2236742 AA genotype was associated with increased pain at all assessed time points.
• Lower CTSG activity was observed in rs2070697 A-allele carriers; no causal link between CTSG activity and pain was found.
• No significant associations were identified for the rs45567233 polymorphism.

Conclusions:

• Specific CTSG gene variants appear to modulate susceptibility to prolonged pain following sternotomy.
• These genetic factors may contribute to individual differences in long-term pain after cardiac surgery.
• Further validation in larger, multi-ethnic cohorts is needed to elucidate mechanisms and guide personalized pain management strategies.