Identification of Genes Expressed in Hyperpigmented Skin Using Meta-Analysis of Microarray Data Sets.

More than 375 genes have been identified that are involved in regulating skin pigmentation and these act during development, survival, differentiation, and/or responses of melanocytes to the environment. Many of these genes have been cloned, and disruptions of their functions are associated with various pigmentary diseases; however, many remain to be identified. We have performed a series of microarray analyses of hyperpigmented compared with less pigmented skin to identify genes responsible for these differences. The rationale and goal for this study was to perform a meta-analysis on these microarray databases to identify genes that may be significantly involved in regulating skin phenotype either directly or indirectly that might not have been identified due to subtle differences by any of these individual studies alone. The meta-analysis demonstrates that 1,271 probes representing 921 genes are differentially expressed at significant levels in the 5 microarray data sets compared, providing new insights into the variety of genes involved in determining skin phenotype. Immunohistochemistry was used to validate two of these markers at the protein level (TRIM63 and QPCT), and we discuss the possible functions of these genes in regulating skin physiology.

Epidermal gene expression and ethnic pigmentation variations among individuals of Asian, European and African ancestry.

Differences in visible skin pigmentation give rise to the wide variation of skin colours seen in racial/ethnic populations. Skin pigmentation is important not only from cosmetic and psychological points of view, but more importantly because of its implications for the risk of all types of skin cancers, on photoaging, etc. Despite differences in those parameters in Caucasian and Asian skin types, they are remarkably similar in their production and distribution of melanins, and the mechanism(s) underlying their different characteristics have remained obscure. In this study, we used microarray analysis of skin suction blisters to investigate molecular differences underlying the determination of pigmentation in various skin types, and we used immunohistochemistry to validate the expression patterns of several interesting targets that were identified. Intriguingly, Caucasian and Asian skins had highly similar gene expression patterns that differed significantly from the pattern of African skin. The results of this study suggest the dynamic interactions of different types of cells in human skin that regulate its pigmentation, reveal that the known pigmentation genes have a limited contribution and uncover a new array of genes, including NINL and S100A4, that might be involved in that regulation.