1. ¹Melanogenix Group, Institute for Molecular Bioscience, University of Queensland, Queensland, Australia
2. ²Queensland Institute of Medical Research, Queensland, Australia
3. ³Dipartimento di Oncologia, Biologia e Genetica, Universita' degli Studi di Genova, Genova, Italy

Correspondence: Assoc. Professor Richard A. Sturm, Melanogenix Group, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia. E-mail: R.Sturm@imb.uq.edu.au

Received 7 March 2008; Revised 23 May 2008; Accepted 5 June 2008; Published online 24 July 2008.

Abstract

Single nucleotide polymorphisms (SNPs) within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P genes have been associated with natural variation of pigmentation traits in human populations. Here, we describe the characterization of human primary melanocytic cells genotyped for polymorphisms within the MATP, NCKX5, or OCA2 loci. On the basis of genotype, these cultured cells reflect the phenotypes observed by others in terms of both melanin content and tyrosinase (TYR) activity when comparing skin designated as either "White" or "Black". We found a statistically significant association of MATP-374L (darker skin) with higher TYR protein abundance that was not observed for any NCKX5-111 or OCA2 rs12913832 allele. MATP-374L/L homozygous strains displayed significantly lower MATP transcript levels compared to MATP-374F/F homozygous cells, but this did not reach statistical significance based on NCKX5 or OCA2 genotype. Similarly, we observed significantly increased levels of OCA2 mRNA in rs12913832-T (brown eye) homozygotes compared to rs12913832-C (blue eye) homozygous strains, which was not observed for MATP or NCKX5 gene transcripts. In genotype–phenotype associations performed on a collection of 226 southern European individuals using these same SNPs, we were able to show strong correlations in MATP-L374F, OCA2, and melanocortin-1 receptor with skin, eye, and hair color variation, respectively.