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 French middle-aged women between 44 and 70 years. A trained dermatologist graded the severity of facial skin photoaging from photographs using Larnier's global scale. Logistic regressions were performed to assess the influence of MC1R polymorphism on severe photoaging (grades 1-3 vs. 4-6), with adjustment for possible confounders (demographic and phenotypic data, and sun exposure intensity).Overall, 35% of the women were wild-type homozygotes, 49% had one variant, 15% had two variants, and 1% had at least one rare variant. After adjustment for possible confounders, the presence of two major diminished function variants was found to be a risk factor for photoaging (adjusted odds ratio=5.61; 95% confidence interval [1.43-21.96]).Our results suggest that genetic variations of MC1R are important determinants for severe photoaging.