Functional MC1R-Gene Variants Are Associated with Increased Risk for Severe Photoaging of Facial Skin

Abstract

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.

Polymorphismes du MC1R et photovieillissement du visage

“…Le but de cette recherche, dont la méthodologie et l'intégralité des résultats ont été rapportés récemment dans le Journal of investigative dermatology [5], était d'étudier les liens entre certains variants du gène MC1R et le photovieillissement global du visage en tenant compte de l'intensité des rides, du relâchement cutané et des troubles pigmentaires.…”

“…Pour les besoins de l'analyse, la variable d'intérêt a été dichotomisée en photovieillissement sévère (oui/non), en regroupant les grades 1 à 3 versus les grades 4 à 6. Les méthodes d'analyse de la séquence et du polymorphisme du MC1R ont été décrites par ailleurs [5]. Le lien entre le polymorphisme du MC1R et l'expression du photovieillissement cutané a été d'abord étudié en regroupant les variants en quatre catégories selon la diminution de la fonction du récepteur : homozygote de type sauvage, un ou deux variants présentant uniquement une diminution mineure de fonction, au moins un variant présentant une diminution majeure de fonction, deux variants présentant une diminution majeure de fonction [13].…”

“…Les variants et les fréquences alléliques sont décrits dans l'article original [5]. Au total, 35 % des femmes étaient homozygotes de type sauvage, 49 % présentaient un seul variant, 15 % deux variants, et 1 % au moins un variant rare.…”

MC1R gene variants involvement in human OCA phenotype

“…The MC1R variants, mainly the RHC alleles were also reported to be associated with increased risk of various types of melanoma [41] and UV induced susceptibility to skin damage [42]. The MC1R variants have been reported to be associated with pigmentary disorders including vitiligo [43], severe photoaging [44], congenital melanocytic nevi [45] and OCA [46]. However, association of MC1R variants with unrelated disorders have also been reported [40].…”

From experimental design to functional gene networks: DNA microarray contribution to skin ageing research

“…Indeed, the intrinsic cell division clock events or the accumulation of damages occurring during natural/intrinsic ageing can be impacted by extrinsic influences, such as reactive oxygen species (ROS), which accelerate the rate of telomere shortening [49]. Conversely, the effects of extrinsic factors might greatly vary among individuals with different genetic background [50][51][52]. The same dose of UV radiation will have different results on two individuals depending on the respective efficiencies of the activities of the catalase or DNA repair genes [53,54].…”