SummaryHuman pigmentation is a polygenic trait which may be shaped by different kinds of gene-gene interactions. Recent studies have revealed that interactive effects between HERC2 and OCA2 may be responsible for blue eye colour determination in humans. Here we performed a population association study, examining important polymorphisms within the HERC2 and OCA2 genes. Furthermore, pooling these results with genotyping data for MC1R, ASIP and SLC45A2 obtained for the same population sample we also analysed potential genetic interactions affecting variation in eye, hair and skin colour. Our results confirmed the association of HERC2 rs12913832 with eye colour and showed that this SNP is also significantly associated with skin and hair colouration. It is also concluded that OCA2 rs1800407 is independently associated with eye colour. Finally, using various approaches we were able to show that there is an interaction between MC1R and HERC2 in determination of skin and hair colour in the studied population sample.

Prediction of physical appearance based on genetic analysis is a very attractive prospect for forensic investigations. Recent studies have proved that there is a significant association between some genetic variants of the melanocortin 1 receptor (MC1R) gene and red hair color. The present study focuses on the potential forensic applicability of variation within this pigment-related gene. Sequencing of the complete MC1R gene was performed on a group of red-haired individuals and controls with different pigmentation. A major role in determination of red hair color is played by two MC1R variants--C451T and C478T. The optimized minisequencing assay for genotyping of the above positions and three other important red hair-related MC1R polymorphisms, C252A, G425A, and G880C was successfully applied to analyze typical forensic specimens. Determination of a homozygous or heterozygous combination can be a good predictor of both red hair color and fair skin of a subject.

In this study, we assessed the role of melanocortin-1 receptor (MC1R) and agouti signalling protein (ASIP) polymorphisms in cutaneous melanoma and basal cell carcinoma (BCC) development in a Polish population. We enrolled 108 patients with skin malignant melanoma (MM) and 102 patients with BCC. The control group consisted of 93 non-red haired patients, without history of skin cancers and 30 healthy individuals with red hair colour (RHC) phenotype. The complete MC1R exon was sequenced and the A8818G polymorphism of the ASIP gene was analysed using the SnaPshot protocol. Selected MC1R mutations were additionally examined using a convenient minisequencing assay. The study confirmed the important role of MC1R R variants in determining physiological variation in hair and skin colour. Our data show that individuals with R mutations had a 3.7-fold increase in melanoma risk and a 3.3-fold increase in BCC risk. Especially, variant R151C significantly increased the risk of both MM and BCC. The studied ASIP polymorphism was found not to be associated with MM or BCC. Stratified analysis showed that the association between MC1R mutations and the risk of MM and BCC was not significantly influenced by subjects' pigmentation characteristics or the 8818G ASIP variant. Further research is necessary, especially involving analysis of interactions between variation in MC1R and other genes, to find out if analysis of MC1R polymorphisms could be of any importance for skin cancer prevention.

Pigmentation is a complex physical trait with multiple genes involved. Several genes have already been associated with natural differences in human pigmentation. The SLC45A2 gene encoding a transporter protein involved in melanin synthesis is considered to be one of the most important genes affecting human pigmentation. Here we present results of an association study conducted on a population of European origin, where the relationship between two non-synonymous polymorphisms in the SLC45A2 gene -rs26722 (E272K) and rs16891982 (L374F) -and different pigmentation traits was examined. The study revealed a significant association between both variable sites and normal variation in hair colour. Only L374F remained significantly associated with hair colour when both SNPs were included in a logistic regression model. No association with other pigmentation traits was detected in this population sample. Our results indicate that the rare allele L374 significantly increases the possibility of having black hair colour (OR = 7.05) and thus may be considered as a future marker for black hair colour prediction.

SummaryA number of genes are considered to affect normal variation in human pigmentation. Recent studies have indicated that OCA2 is the crucial gene involved in the high variation of iris colour present among populations of European descent. In this study, eleven polymorphisms of the OCA2 gene were examined in search of their association with different pigment traits. The evolutionary tree scanning method indicated that the strongest phenotypic eye colour variation is associated with the branch defined by nonsynonymous change rs1800407, which refers to amino acid causing change Arg419Gln located in exon 13. Single SNP analysis indicated that allele 419Gln is associated with green/hazel iris colour (p < 0.001). According to tree scanning analysis, the proportion of eye colour variation explained by this nucleotide position is merely 4%. Thus, additional variation present in the OCA2 gene and perhaps some other pigment related genes must be taken into account in order to explain the high phenotypic variation in iris colour.