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In this study, 33 single nucleotide polymorphisms (SNPs) in known pigmentation genes were tested for association to objective spectrophotometric reflectance measurements of the upper-inner arm and the buttock in 188 unrelated Danes. The 188 Danes were typed for 33 SNPs by two multiplex PCRs, two multiplex single base extension reactions and capillary electrophoresis. To further investigate the role of the SNPs, their allelic distribution was compared to those in a population of 36 Somalis. Four MC1R SNP alleles (R151C, R160W, D294H and 29insA) showed significant associations to light skin pigmentation in individuals who were either homozygous or compound heterozygous. This confirms the regulatory role of MC1R in skin pigmentation. SNP loci in SLC45A2 , SLC24A5 and TYR showed large allele frequency differences between Somalis and Danes, which suggested a possible role in skin pigmentation. The average buttock pigmentation was significantly lighter than the average upper-inner arm pigmentation. Therefore, the buttock reflectance measurements better resemble the constitutive skin colour compared to upper-inner arm reflectance measurements and will be used in future studies.

Background Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS) have been the ideal strategy to identify new common, low-penetrance susceptibility loci. In this case–control study, we try to validate in our population nine melanoma associated markers selected from published GWAS in melanoma predisposition. Methods We genotyped the 9 markers corresponding to 8 genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and 347 controls from a Spanish population using KASPar probes. Genotypes were analyzed by logistic regression and adjusted by phenotypic characteristics. Results We confirm the protective role in MM of the rs3219090 located on the PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4 gene was associated with protection to develop MM for the dominant model (p-value 0.037). We have also observed an association of this SNP with both lentigines (p-value 0.014) and light eye color (p-value 3.76 × 10-4). Furthermore, we detected a novel association with rs1485993, located on the CCND1 gene, and dark eye color (p-value 4.96 × 10-4). Finally, rs1801516, located on the ATM gene, showed a trend towards a protective role in MM similar to the one firstly described in a GWAS study. Conclusions To our knowledge, this is the first time that these SNPs have been associated with MM in a Spanish population. We confirmed the proposed role of rs3219090, located on the PARP1 gene, and rs12203592, located on the IRF4 gene, as protective to MM along the same lines as have previous genome-wide associated works. Finally, we have seen associations between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming previous results for the IRF4 gene and presenting novel data for the last two, suggesting that pigmentation characteristics correlated with eye color are potential mediators between PARP1 and MM protection.

Brown and blue eye colours are primarily explained by the single nucleotide polymorphism (SNP) HERC2 rs12913832. However, the genetics of eye colours that appear to be neither blue nor brown are not well understood. In this study, 230 unrelated Italian individuals were typed for 32 SNP loci in pigmentary genes. High resolution digital images of the participants' eyes were taken and the iris region was successfully extracted with the use of the custom designed software Digital Iris Analysis Tool (DIAT) from 218 of the 230 (95%) images. The software counted the numbers of blue and brown pixels in the iris region and calculated a Pixel Index of the Eye (PIE-score) that described the eye colours quantitatively. The PIE-score ranged from −1 to 1 (brown to blue). We investigated the association of the PIE-scores extracted from the eye images with the genotypes of the 32 pigmentary SNPs. We observed a statistically significant association between the PIE-scores and the SNP loci rs12913832, rs4778241, rs7495174 in the HERC2 / OCA2 region and the locus rs16891982 in SLC45A2 .