Haddadeen Ciara, Lai Chester, Cho Shin-Young, Healy Eugene
Dermatopharmacology, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton, UK; Dermatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Exp Dermatol. 2015 Jan;24(1):5-9. doi: 10.1111/exd.12540. Epub 2014 Nov 11.
The melanocortin 1 receptor (MC1R) gene encodes for a seven-pass transmembrane receptor primarily expressed on melanocytes and melanoma cells. Single nucleotide polymorphisms (SNPs, also termed variants) in MC1R frequently cause red hair, fair skin and are associated with melanoma and keratinocyte-derived skin cancer development. Activation of wild-type (WT) MC1R in skin assists cutaneous photoprotection whereas reduced MC1R signalling, seen with MC1R variants, impairs ultraviolet radiation (UVR)-protective responses. As ancestral humans migrated out of Africa, the evolutionary advantage of MC1R variants may have related to improved cutaneous vitamin D synthesis and higher birthweight reported with certain MC1R variants. Reduced photoprotection secondary to MC1R dysfunction involves pigmentary and non-pigmentary mechanisms (reduced DNA repair, effects on cell proliferation and possibly immunological parameters), leading to clonal expansion of mutated cells within skin and subsequent carcinogenesis. Recent investigations suggest an association between MC1R genotype and vitiligo, with preliminary evidence that a MC1R agonist, [Nle4-D-Phe7]-alpha-MSH, in combination with UVB, assists repigmentation. Future development of compounds to correct defective MC1R responses secondary to MC1R variants could result in photoprotective benefits for fair-skinned individuals and reduce their skin cancer risk.
黑皮质素1受体（MC1R）基因编码一种七次跨膜受体，主要在黑素细胞和黑色素瘤细胞上表达。MC1R中的单核苷酸多态性（SNP，也称为变体）常导致红发、白皙皮肤，并与黑色素瘤和角质形成细胞源性皮肤癌的发生有关。皮肤中野生型（WT）MC1R的激活有助于皮肤光保护，而MC1R变体导致的MC1R信号传导减少会损害紫外线（UVR）防护反应。随着原始人类迁出非洲，MC1R变体的进化优势可能与某些MC1R变体报告的皮肤维生素D合成改善和出生体重增加有关。MC1R功能障碍继发的光保护作用降低涉及色素性和非色素性机制（DNA修复减少、对细胞增殖的影响以及可能的免疫参数），导致皮肤内突变细胞的克隆扩增和随后的致癌作用。最近的研究表明MC1R基因型与白癜风之间存在关联，初步证据显示MC1R激动剂[Nle4-D-Phe7]-α-MSH与UVB联合使用有助于色素再生。未来开发用于纠正MC1R变体继发的MC1R反应缺陷的化合物，可能会为皮肤白皙的个体带来光保护益处，并降低他们患皮肤癌的风险。
