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

Br J Dermatol. 2007 Dec;157(6):1230-4. doi: 10.1111/j.1365-2133.2007.08209.x. Epub 2007 Oct 4.

Abstract

Background: 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.

Objectives: To investigate whether MC1R genotype influences erythemal sensitivity to psoralen-UVA photochemotherapy (PUVA) in patients with psoriasis and other common skin diseases.

Methods: 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.

Results: 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).

Conclusions: Our data demonstrate that MC1R genotype influences PUVA erythemal sensitivity in patients with psoriasis and other common skin diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dose-Response Relationship, Radiation
  • Erythema / etiology*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Hair Color / genetics*
  • Humans
  • Male
  • PUVA Therapy / adverse effects*
  • Psoriasis / drug therapy
  • Receptor, Melanocortin, Type 1 / genetics*
  • Skin / radiation effects
  • Skin Neoplasms / genetics*
  • Skin Pigmentation / genetics*
  • Ultraviolet Rays / adverse effects

Substances

  • Receptor, Melanocortin, Type 1