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


OBJECTIVE
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.
Smith
G
G
Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. gillian.smith@cancer.org.uk
Wilkie
M J V
MJ
Deeni
Y Y
YY
Farr
P M
PM
Ferguson
J
J
Wolf
C R
CR
Ibbotson
S H
SH
D000328:Adult; D004307:Dose-Response Relationship, Radiation; D004890:Erythema / Q000209:etiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006200:Hair Color / Q000235:genetics*; D006801:Humans; D008297:Male; D011701:PUVA Therapy / Q000009:adverse effects*; D011565:Psoriasis / Q000188:drug therapy; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012867:Skin / Q000528:radiation effects; D012878:Skin Neoplasms / Q000235:genetics*; D012880:Skin Pigmentation / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects
D044102:Receptor, Melanocortin, Type 1