Melanocortin 1 receptor (MC1R) genotype influences erythemal sensitivity to psoralen–ultraviolet A photochemotherapy

Abstract

The melanocortin 1 receptor (MC1R) is a highly polymorphic G protein-coupled receptor. Inheritance of various MC1R alleles has been associated with a red hair/fair skin phenotype, increased incidence of skin cancer and altered sensitivity to ultraviolet (UV) radiation. To investigate whether MC1R genotype influences erythemal sensitivity to psoralen-UVA photochemotherapy (PUVA) in patients with psoriasis and other common skin diseases. Patients (n = 111) about to start PUVA were recruited to the study. Erythemal responses were assessed visually at 72 h and 96 h following PUVA by assessment of the minimal phototoxic dose (MPD). MC1R genotype was determined by direct sequencing. Inheritance of the MC1R Arg(151)Cys allele was associated with a red hair phenotype (odds ratio 25.19, P = 0.0004). In contrast, inheritance of the Val(60)Leu and Arg(163)Gln SNPs was associated with increased PUVA erythemal sensitivity (reduced MPD) 72 h following treatment in all patients (n = 111; Val(60)Leu chi(2) = 5.764, P = 0.016; Arg(163)Gln chi(2) = 5.469, P = 0.019) and in a subset of patients with psoriasis (n = 55; Val(60)Leu chi(2) = 4.534, P = 0.033; Arg(163)Gln chi(2) = 7.298, P = 0.007). Inheritance of two or more MC1R SNPs was also associated with increased PUVA erythemal sensitivity (reduced MPD) in both patient groups (n = 111; chi(2) = 8.166, P = 0.017; n = 55; chi(2) = 10.303, P = 0.016). Our data demonstrate that MC1R genotype influences PUVA erythemal sensitivity in patients with psoriasis and other common skin diseases.