The objective of this study was to assess the association between melanocortin-1 
receptor (MC1R) variants and the severity of facial skin photoaging. The study 
population comprised 530 middle-aged French women. A trained dermatologist 
graded the severity of facial skin photoaging from photographs using a global 
scale. Logistic regressions were performed to assess the influence of MC1R 
polymorphisms on severe photoaging with adjustment for possible confounders 
(demographic and phenotypic data and sun exposure intensity). Among the fifteen 
MC1R variants identified, the nine most common were V60L, V92M, R151C, R160W, 
R163Q, R142H, D294H, D84E, and I155T. One hundred and eighty-five individuals 
(35%) were WT homozygotes, 261 (49%) had one common variant, 78 (15%) had two 
common variants, and six (1%) had at least one rare variant. After adjustment 
for possible confounders, the presence of two common variants was already a risk 
factor for severe photoaging (AOR (95% confidence interval): 2.33 (1.17-4.63)). 
This risk reached 5.61 (1.43-21.96) when two major diminished-function variants 
were present. Surprisingly, the minor variant, V92M, was associated with 
increased risk of photoaging (2.57 (1.23-5.35)). Our results suggest that 
genetic variations of MC1R are important determinants for severe photoaging.