TACR1 gene polymorphism and sex differences in postoperative nausea and vomiting

Area of Science:

• Pharmacogenetics
• Neuroscience
• Genetics

Background:

• Postoperative nausea and vomiting (PONV) exhibits significant sex-based differences.
• The TACR1 gene, encoding neurokinin-1 (NK1) receptors, is a potential candidate for mediating these sex differences in PONV.
• Single nucleotide polymorphisms (SNPs) within TACR1 may contribute to variations in PONV susceptibility.

Purpose of the Study:

• To investigate the association between genetic variations in the TACR1 gene and sex differences in postoperative nausea and vomiting (PONV).
• To identify specific SNPs and haplotypes within TACR1 that correlate with PONV incidence and severity.

Main Methods:

• Genotyping of 32 selected single nucleotide polymorphisms (SNPs) in the TACR1 gene using Sanger sequencing.
• Evaluation of the incidence and severity of postoperative nausea and vomiting in 200 patients undergoing lower abdominal surgery.
• Statistical analysis to determine associations between SNPs, haplotypes, and PONV outcomes.

Main Results:

• The rs3755468-SNP in the TACR1 gene was significantly associated with both the incidence and severity of PONV (p=0.016).
• A specific TT haplotype, including rs3755468, demonstrated a significant association with reduced PONV incidence and severity in female patients (p=0.03).
• The rs3755468-SNP is located in a region with predicted oestrogen response elements and DNase I hypersensitive sites.

Conclusions:

• Single nucleotide polymorphisms in the TACR1 gene are associated with sex differences observed in postoperative nausea and vomiting.
• These genetic variations may play a role in elucidating the underlying mechanisms of sex-based disparities in PONV.
• The rs3755468-SNP and the TT haplotype represent potential genetic markers for PONV risk stratification.