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

Evidence suggests that redheaded individuals react differently to local anesthetics, but there is no defined human genotype associated with local anesthetic response. As red hair has been associated with unique mutations of the melanocortin-1 receptor (MC1R), we tested the hypothesis that local anesthetic onset and duration of action were significantly modified in red haired individuals as related to the single nucleotide polymorphism (SNP) genotype.

Ninety-two participants between the ages of 18 and 65 years were enrolled and assigned to one of four experimental groups: lidocaine-redhead, lidocaine-brunette hair, bupivacaine-redhead, and bupivacaine-brunette hair. Onset and duration of action were quantified in response to sharp sensation. Sputum samples were collected, gDNA was extracted and subjected to the Illumina CoreExome-24 SNP array (Illumina, San Diego, California). Twenty-five MC1R sequence polymorphisms were analyzed. A two-way analysis of variance (ANOVA) test was used to examine treatment and hair color effects, and their interaction on onset and duration time respectively; P ≤ .05 was considered statistically significant.

Overall mean onset of action was statistically significant (P = .042) when comparing red hair to brunette responses between anesthesia (lidocaine versus bupivacaine: 2.68 ± 0.28 minutes versus 3.60 ± 0.30 minutes, and 4.46 ± 0.49 minutes versus 5.14 ± 0.46 minutes, respectively). The redhead mean duration times were statistically shorter (P = .007) than brunettes (lidocaine and bupivacaine: 72.5 ± 6.3 min versus 97.6 ± 12.1 min, and 367.7 ± 21.4 minutes versus 455.5 ± 30.2 minutes, respectively). There were no statistical interactions between treatment and hair color on either onset or duration (P = .761 and P = .120, respectively). Interestingly, bupivacaine-injected redhead participants did show a significantly shorter duration (P = .004). Of 25 SNPs from MC1R assayed from the Illumina CoreExome-24 array, two missense mutations at loci rs1805007 (R151C) and rs1805008 (R160W) significantly predicted phenotypic responses to local analgesics. A two-way ANOVA indicated that these SNPs were significantly associated with reduced onset and duration time (P = .014, P = .047, respectively). Additionally, χ2 tests demonstrated a significantly strong correlation between red hair and these SNPs: R151C (P < .001, Power = 1.000) and R160W (P = .016, Power = 0.732).

To our knowledge there are no published studies that associate the effect of hair color with local anesthetic function on onset and duration of action via SNP genotyping. The SNP genotyping reaffirmed functional results, and points to the complimentary impact that precision medicine will have on clinical decision making and patient comfort with future studies to unravel the degree to which SNPs affect these responses.