Local Anesthetic Duration, Not Onset, Linked to MC1R Genotype in Redheads and Brunettes

Area of Science:

• Pharmacogenetics
• Anesthesiology
• Genetics

Background:

• Red hair is associated with unique melanocortin-1 receptor (MC1R) mutations.
• Previous evidence suggests redheads may have altered responses to local anesthetics.
• No human genotype has been definitively linked to local anesthetic response variations.

Purpose of the Study:

• To test the hypothesis that local anesthetic onset and duration are modified in redheads based on MC1R single nucleotide polymorphism (SNP) genotype.
• To investigate the association between MC1R SNPs and local anesthetic effects.

Main Methods:

• 92 participants (redhead and brunette) were enrolled in four groups (lidocaine-redhead, lidocaine-brunette, bupivacaine-redhead, bupivacaine-brunette).
• Onset and duration of local anesthetic action were quantified.
• gDNA was extracted from sputum samples, and 25 MC1R polymorphisms were analyzed using SNP genotyping (Illumina CoreExome-24 array).
• Statistical analysis included two-way ANOVA and chi-squared tests.

Main Results:

• Redheads experienced statistically significant faster onset (P = .042) and shorter duration (P = .007) of local anesthetics compared to brunettes.
• Bupivacaine-injected redheads showed a significantly shorter duration (P = .004).
• Two MC1R missense mutations (rs1805007 and rs1805008) were significantly associated with reduced onset and duration times (P = .014, P = .047).
• Strong correlations were found between red hair and these specific SNPs (R151C, P < .001; R160W, P = .016).

Conclusions:

• This study is the first to associate hair color, local anesthetic function, and SNP genotyping.
• SNP genotyping confirmed functional results, highlighting the role of MC1R gene variations in anesthetic response.
• Findings support the integration of precision medicine for enhanced clinical decision-making and patient comfort.