Journal of Human Genetics

, Volume 53, Issue 11–12, pp 966–971 | Cite as

Association of the SLC45A2 gene with physiological human hair colour variation

  • Wojciech Branicki
  • Urszula Brudnik
  • Jolanta Draus-Barini
  • Tomasz Kupiec
  • Anna Wojas-Pelc
Original Article

Abstract

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.

Keywords

Pigmentation SLC45A2 Association study E272K L374F Phenotype prediction 

References

  1. Akey JM, Wang H, Xiong M, Wu H, Liu W, Shriver MD, Jin L (2001) Interaction between the melanocortin-1 receptor and P genes contributes to inter-individual variation in skin pigmentation phenotypes in a Tibetan population. Hum Genet 108:516–520PubMedCrossRefGoogle Scholar
  2. Bennett DC, Lamoreux ML (2003) The color loci of mice—a genetic century. Pigment Cell Res 16:333–344PubMedCrossRefGoogle Scholar
  3. Bonilla C, Boxill LA, Donald SA, Williams T, Sylvester N, Parra EJ, Dios S, Norton HL, Shriver MD, Kittles RA (2005) The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans. Hum Genet 116:402–406PubMedCrossRefGoogle Scholar
  4. Branicki W, Brudnik U, Wojas-Pelc A (2005) Genetic prediction of pigmentary traits in forensic studies. Probl Forensic Sci 64:343–357Google Scholar
  5. Branicki W, Brudnik U, Kupiec T, Wolanska-Nowak P, Wojas-Pelc A (2007) Determination of phenotype associated SNPs in the MC1R gene. J Forensic Sci 52:349–354PubMedCrossRefGoogle Scholar
  6. Branicki W, Brudnik U, Kupiec T, Wolańska-Nowak P, Szczerbińska A, Wojas-Pelc A (2008) Association of polymorphic sites in the OCA2 gene with eye colour using the tree scanning method. Ann Human Genet 72:184–192CrossRefGoogle Scholar
  7. Brudnik U, Branicki W, Wojas-Pelc A, Kanas P (2008) The contribution of melanocortin 1 receptor gene polymorphisms and the agouti signalling protein gene 8818A>G polymorphism to cutaneous melanoma and basal cell carcinoma in a Polish population. Exp Dermatol. doi: 10.1111/j.1600-0625.2008.00760.x
  8. Costin GE, Valencia JC, Vieira WD, Lamoreux ML, Hearing VJ (2003) Tyrosinase processing and intracellular trafficking is disrupted in mouse primary melanocytes carrying the underwhite (uw) mutation A model for oculocutaneous albinism (OCA) type 4. J Cell Sci 116:3203–3212PubMedCrossRefGoogle Scholar
  9. Duffy DL, Montgomery GW, Chen W, Zhao ZZ, Le L, James MR, Hayward NK, Martin NG, Sturm RA (2007) A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. Am J Hum Genet 80:241–252PubMedCrossRefGoogle Scholar
  10. Eiberg H, Troelsen J, Nielsen M, Mikkelsen A, Mengel-From J, Kjaer KW, Hansen L (2008) Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. Hum Genet 123(2):177–187PubMedCrossRefGoogle Scholar
  11. Excoffier L, Laval G, Schneider S (2005) Arlequin ver 30: an integrated software package for population genetics data analysis. Evol Bioinform Online 1:47–50PubMedGoogle Scholar
  12. Fernandez LP, Milne RL, Pita G, Avilés JA, Lázaro P, Benítez J, Ribas G (2008) SLC45A2: a novel malignant melanoma-associated gene. Hum Mutat 29(9):1161–1167. doi:10.1002/humu.20804 PubMedCrossRefGoogle Scholar
  13. Fitzpatrick TB (1988) The validity and practicability of sun-reactive skin types I through VI. Arch Dermatol 124:869–871PubMedCrossRefGoogle Scholar
  14. Frudakis T, Thomas M, Gaskin Z, Venkateswarlu K, Chandra KS, Ginjupalli S, Gunturi S, Natrajan S, Ponnuswamy VK, Ponnuswamy KN (2003) Sequences associated with human iris pigmentation. Genetics 165:2071–2083PubMedGoogle Scholar
  15. Gorroochurn P, Hodge SE, Heiman GA, Durner M, Greenberg DA (2007) Non-replication of association studies: “pseudo-failures” to replicate? Genet Med 9:325–331PubMedCrossRefGoogle Scholar
  16. Grimes EA, Noake PJ, Dixon L, Urquhart A (2001) Sequence polymorphism in the human melanocortin 1 receptor gene as an indicator of the red hair phenotype. Forensic Sci Int 122:124–129PubMedCrossRefGoogle Scholar
  17. Graf J, Hodgson R, van Daal A (2005) A single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation. Hum Mutat 25:278–284PubMedCrossRefGoogle Scholar
  18. Graf J, Voisey J, Hughes I, van Daal A (2007) Promoter polymorphisms in the MATP (SLC45A2) gene are associated with normal human skin color variation. Hum Mutat 28:710–717PubMedCrossRefGoogle Scholar
  19. Han J, Kraft P, Nan H, Guo Q, Chen C, Qureshi A, Hankinson SE, Hu FB, Duffy DL, Zhao ZZ, Martin NG, Montgomery GW, Hayward NK, Thomas G, Hoover RN, Chanock S, Hunter DJ (2008) A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genet 16(5):e1000074CrossRefGoogle Scholar
  20. Harding RM, Healy E, Ray AJ, Ellis NS, Flanagan N, Todd C, Dixon C, Sajantila A, Jackson IJ, Birch-Machin MA, Rees JL (2000) Evidence for variable selective pressures at MC1R. Am J Hum Genet 66:1351–1361PubMedCrossRefGoogle Scholar
  21. Inagaki K, Suzuki T, Shimizu H, Ishii N, Umezawa Y, Tada J, Kikuchi N, Takata M, Takamori K, Kishibe M, Tanaka M, Miyamura Y, Ito S, Tomita Y (2004) Oculocutaneous albinism type 4 is one of the most common types of albinism in Japan. Am J Hum Genet 74:466–471PubMedCrossRefGoogle Scholar
  22. Inagaki K, Suzuki T, Ito S, Suzuki N, Adachi K, Okuyama T, Nakata Y, Shimizu H, Matsuura H, Oono T, Iwamatsu H, Kono M, Tomita Y (2006) Oculocutaneous albinism type 4: six novel mutations in the membrane-associated transporter protein gene and their phenotypes. Pigment Cell Res 19:451–453PubMedCrossRefGoogle Scholar
  23. Jablonski N (2004) The evolution of human skin and skin color. Annu Rev Anthropol 2004:585–624CrossRefGoogle Scholar
  24. Kanetsky PA, Swoyer J, Panossian S, Holmes R, Guerry D, Rebbeck TR (2002) A polymorphism in the agouti signaling protein gene is associated with human pigmentation. Am J Hum Genet 70:770–775PubMedCrossRefGoogle Scholar
  25. Kanetsky PA, Rebbeck TR, Hummer AJ, Panossian S, Armstrong BK, Kricker A, Marrett LD, Millikan RC, Gruber SB, Culver HA, Zanetti R, Gallagher RP, Dwyer T, Busam K, From L, Mujumdar U, Wilcox H, Begg CB, Berwick M (2006) Population-based study of natural variation in the melanocortin-1 receptor gene and melanoma. Cancer Res 66:9330–9337PubMedCrossRefGoogle Scholar
  26. Kayser M, Liu F, Janssens AC, Rivadeneira F, Lao O, van Duijn K, Vermeulen M, Arp P, Jhamai MM, van Ijcken WF, den Dunnen JT, Heath S, Zelenika D, Despriet DD, Klaver CC, Vingerling JR, de Jong PT, Hofman A, Aulchenko YS, Uitterlinden AG, Oostra BA, van Duijn CM (2008) Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene. Am J Hum Genet 82:411–423PubMedCrossRefGoogle Scholar
  27. Lao O, de Gruijter JM, van Duijn K, Navarro A, Kayser M (2007) Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms. Ann Hum Genet 71:354–369PubMedCrossRefGoogle Scholar
  28. Moore JH (2003) The ubiquitous nature of epistasis in determining susceptibility to common human diseases. Hum Hered 56:73–82PubMedCrossRefGoogle Scholar
  29. Neale BM, Sham PC (2004) The future of association studies: gene-based analysis and replication. Am J Hum Genet 75:353–362PubMedCrossRefGoogle Scholar
  30. Oetting WS, Garrett SS, Brott M, King RA (2005) P gene mutations associated with oculocutaneous albinism type II (OCA2). Hum Mutat 25:323–329PubMedCrossRefGoogle Scholar
  31. Pastorino L, Cusano R, Bruno W, Lantieri F, Origone P, Barile M, Gliori S, Shepherd GA, Sturm RA, Bianchi-Scarra G (2004) Novel MC1R variants in Ligurian melanoma patients and controls. Hum Mutat 24:103–112PubMedCrossRefGoogle Scholar
  32. Rebbeck TR, Kanetsky PA, Walker AH, Holmes R, Halpern AC, Schuchter LM, Elder DE, Guerry D (2002) P gene as an inherited biomarker of human eye color. Cancer Epidemiol Biomarkers Prev 11:782–784PubMedGoogle Scholar
  33. Rees JL (2003) Genetics of hair and skin color. Annu Rev Genet 37:67–90PubMedCrossRefGoogle Scholar
  34. Rees JL (2004) The genetics of sun sensitivity in humans. Am J Hum Genet 75:739–751PubMedCrossRefGoogle Scholar
  35. Rundshagen U, Zühlke C, Opitz S, Schwinger E, Käsmann-Kellner B (2004) Mutations in the MATP gene in five German patients affected by oculocutaneous albinism type 4. Hum Mutat 23:106–110PubMedCrossRefGoogle Scholar
  36. Sabeti PC, Varilly P, Fry B, Lohmueller J, Hostetter E, Cotsapas C, Xie X, Byrne EH et al (2007) Genome-wide detection and characterization of positive selection in human populations. Nature 449:913–918PubMedCrossRefGoogle Scholar
  37. Savage SA, Gerstenblith MR, Goldstein AM, Mirabello L, Fargnoli MC, Peris K, Landi MT (2008) Nucleotide diversity and population differentiation of the melanocortin 1 receptor gene, MC1R. BMC Genet 10:31CrossRefGoogle Scholar
  38. Soejima M, Tachida H, Ishida T, Sano A, Koda Y (2006) Evidence for recent positive selection at the human AIM1 locus in a European population. Mol Biol Evol 23:179–188PubMedCrossRefGoogle Scholar
  39. Sturm RA, Duffy DL, Zhao ZZ, Leite FP, Stark MS, Hayward NK, Martin NG, Montgomery GW (2008) A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am J Hum Genet 82:424–431PubMedCrossRefGoogle Scholar
  40. Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Magnusson KP, Manolescu A, Karason A, Palsson A, Thorleifsson G, Jakobsdottir M, Steinberg S, Pálsson S, Jonasson F, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Aben KK, Kiemeney LA, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K (2007) Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat Genet 39:1443–1452PubMedCrossRefGoogle Scholar
  41. Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Jakobsdottir M, Steinberg S, Gudjonsson SA, Palsson A, Thorleifsson G, Pálsson S, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Aben KK, Vermeulen SH, Goldstein AM, Tucker MA, Kiemeney LA, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K (2008) Two newly identified genetic determinants of pigmentation in Europeans. Nat Genet 40(7):835–837. doi:10.1038/ng.160 PubMedCrossRefGoogle Scholar
  42. Voisey J, Van Daal A (2002) Agouti: from mouse to man, from skin to fat. Pigment Cell Res 15:10–18PubMedCrossRefGoogle Scholar
  43. Yuasa I, Umetsu K, Watanabe G, Nakamura H, Endoh M, Irizawa Y (2004) MATP polymorphisms in Germans and Japanese: the L374F mutation as a population marker for Caucasoids. Int J Legal Med 118:364–366PubMedCrossRefGoogle Scholar
  44. Yuasa I, Umetsu K, Harihara S, Kido A, Miyoshi A, Saitou N, Dashnyam B, Jin F, Lucotte G, Chattopadhyay PK, Henke L, Henke J (2006) Distribution of the F374 allele of the SLC45A2 (MATP) gene and founder-haplotype analysis. Ann Hum Genet 70:802–811PubMedCrossRefGoogle Scholar

Copyright information

© The Japan Society of Human Genetics and Springer 2008

Authors and Affiliations

  • Wojciech Branicki
    • 1
  • Urszula Brudnik
    • 2
  • Jolanta Draus-Barini
    • 1
  • Tomasz Kupiec
    • 1
  • Anna Wojas-Pelc
    • 2
  1. 1.Section of Forensic GeneticsInstitute of Forensic ResearchKrakowPoland
  2. 2.Department of DermatologyCollegium Medicum of the Jagiellonian UniversityKrakowPoland

Personalised recommendations