Selected gene polymorphisms effect on skin and hair pigmentation in Polish children at the prepubertal age

Background: Human pigmentation, similarly as many other biological features, changes in the course of post-natal ontogenesis, while in case of hair, pigmentation changes are more distinctive than in the skin or the iris. It is therefore extremely important to identify the genes, involved in the constitution of human pigmentation features at various stages of ontogenesis. Results of this type of analyses are of high practical significance in forensic study because they enable to create mathematical tools, allowing for prediction of the pigmentation phenotype, based on DNA studies. Aim: The objective of the investigation was finding out whether the genes, associated with pigmentation of adult subjects, differentiated in any way the newly forming pigmentation phenotype in Polish prepubertal children. Material and methods: The study encompassed Polish children, aged 7 to 10 years, without any abnormalities in skin or hair pigmentation. A total of 245 children were examined. Constitutive skin pigmentation according to skin melanin index (SMI) was evaluated, using a dermaspectrometer, and classified into three groups based on the reference values of 25 and 75 percentile for Polish children. Hair colors were evaluated by means of the descriptive Fischer-Saller scale and classified by a division of color variants (as accepted in that scale) (light blonde, blonde, dark blonde, brown and dark brown). In saliva samples, collected from the children, five (5) single nucleotide polymorphisms were identified: SNPs: rs1800401 (OCA2-15q11.2-q12), rs35264875 (TPCN2-11q13.3), rs16891982 (SLC45A2-5p13.2), rs12913832 (HERC2-15q13) and rs1805007 (MC1R-16q24.3). An association between each allele of verified genotype and skin and hair color phenotypes was assessed, using the z-statistic and associated p-value. The quality of classifiers was evaluated by 10-fold stratified cross-validation and was characterized by the area under the receiver operating characteristic curve (AUC). Results: Light skin pigmentation phenotype (SMI<25 percentile) was associated with rs1805007 (MC1R) (allelic OR=3.95; 95% Cl:1.20-12.99; p=0.0235), while the dark shade of the skin (SMI>75 percentile) with rs16891982 (SLC45A2) (allelic OR =14.37; 95% Cl: 1.78-115.88; p=0.0123). The probability of dark hair (brown and dark brown) in childhood was increased by T rs12913832 allele (HERC2) (OR=3.63); 95% Cl: 2.25-5.85; p < 0.0001) and dependent on it - rs1800401 (OCA2) (OR=6.31; 95% Cl: 1.74-22.91; p=0.0051). Other SNPs were not significantly associated with skin and hair color but improved prediction of these features. Conclusions: From the five gene polymorphisms analysed in Polish children the strongest correlation with hair color has the rs12913832 (HERC2) and with skin color - rs16891982 (SLC45A2). Therefore, the above-mentioned polymorphisms may be used as components of potential models, used to predict pigmentation features in European origin children in prepubertal age. To improve predictive value of the potential scoring model for hair color, the following should be additionally included: rs1800401 (OCA2), rs35264875 (TPCN2) and rs1805007 (MC1R), while for skin color: rs12913832 (HERC2) and rs1805007 (MC1R).