The relation between melanocortin 1 receptor genotype and experimentally assessed ultraviolet radiation sensitivity

Pigmentary phenotype is a key determinant of an individual's response to ul traviolet radiation with the presence of phaeomelanin thought to be of part icular importance. Reports of minimal erythema testing, however, have faile d to show a consistent difference between skin type I and other skin types. The melanocortin 1 receptor is a key genetic determinant of the cutaneous response to ultraviolet radiation. In this study we investigate the relatio n between experimentally induced erythemal response to ultraviolet radiatio n and the melanocortin 1 receptor genotype. Phototesting was performed in 2 0 redheads and 20 nonredheaded subjects, the majority of whom were also scr eened for the presence of melanocortin 1 receptor variants. The majority of redheads sequenced (89%) had two melanocortin 1 receptor variants previous ly found to be associated with red hair compared to none of the controls. T here was no significant difference between the groups in minimal erythema d ose: the median minimal erythema dose in redheads was 44 mJ per cm(2) (inte rquartile range 34-56) and in the nonredheaded group was 40 mJ per cm 2 (in terquartile range 40-56). Objective measurements of ultraviolet-B-induced e rythema were performed using reflectance instrument measurements of erythem a intensity and dose-response curves constructed for each subject. The slop e of the dose-response curve in the redheaded group was statistically great er than in the nonredheaded group (median in redheads 4.08 vs 3.56 for cont rols, 95% confidence interval for the difference between the medians being 0.01-1.23, p = 0.043). In addition the ratio D-0.05:D-0.025 was significant ly lower for the redheaded group (median in redheads 1.22, interquartile ra nge 1.18-1.26; median in nonreds 1.28, interquartile range 1.23-1.32; p <0. 05). Thus, although the minimal erythema dose values were not different, su bjects with red hair develop greater intensity of erythema than nonredheade d individuals when doses greater than the minimal erythema dose are given. Importantly, when analyzed by genotype alone rather than phenotype, the slo pe of the erythema dose-response differed between those persons who were ho mozygous or heterozygous mutants and wildtype/pseudo-wildtype (p = 0.026).