Tags

Type your tag names separated by a space and hit enter

Interactive effects of MC1R and OCA2 on melanoma risk phenotypes.
Hum Mol Genet 2004; 13(4):447-61HM

Abstract

The relationships between MC1R gene variants and red hair, skin reflectance, degree of freckling and nevus count were investigated in 2331 adolescent twins, their sibs and parents in 645 twin families. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. Of nine MC1R variant alleles assayed, four common alleles were strongly associated with red hair and fair skin (Asp84Glu, Arg151Cys, Arg160Trp and Asp294His), with a further three alleles having low penetrance (Val60Leu, Val92Met and Arg163Gln). These variants were separately combined for the purposes of this analysis and designated as strong 'R' (OR=63.3; 95% CI 31.9-139.6) and weak 'r ' (OR=5.1; 95% CI 2.5-11.3) red hair alleles. Red-haired individuals are predominantly seen in the R/R and R/r groups with 67.1 and 10.8%, respectively. To assess the interaction of the brown eye color gene OCA2 on the phenotypic effects of variant MC1R alleles we included eye color as a covariate, and also genotyped two OCA2 SNPs (Arg305Trp and Arg419Gln), which were confirmed as modifying eye color. MC1R genotype effects on constitutive skin color, freckling and mole count were modified by eye color, but not genotype for these two OCA2 SNPs. This is probably due to the association of these OCA2 SNPs with brown/green not blue eye color. Amongst individuals with a R/R genotype (but not R/r), those who also had brown eyes had a mole count twice that of those with blue eyes. This suggests that other OCA2 polymorphisms influence mole count and remain to be described.

Authors+Show Affiliations

Queensland Insititute of Medical Research, Brisbane, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14709592

Citation

Duffy, David L., et al. "Interactive Effects of MC1R and OCA2 On Melanoma Risk Phenotypes." Human Molecular Genetics, vol. 13, no. 4, 2004, pp. 447-61.
Duffy DL, Box NF, Chen W, et al. Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Hum Mol Genet. 2004;13(4):447-61.
Duffy, D. L., Box, N. F., Chen, W., Palmer, J. S., Montgomery, G. W., James, M. R., ... Sturm, R. A. (2004). Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Human Molecular Genetics, 13(4), pp. 447-61.
Duffy DL, et al. Interactive Effects of MC1R and OCA2 On Melanoma Risk Phenotypes. Hum Mol Genet. 2004 Feb 15;13(4):447-61. PubMed PMID: 14709592.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. AU - Duffy,David L, AU - Box,Neil F, AU - Chen,Wei, AU - Palmer,James S, AU - Montgomery,Grant W, AU - James,Michael R, AU - Hayward,Nicholas K, AU - Martin,Nicholas G, AU - Sturm,Richard A, Y1 - 2004/01/06/ PY - 2004/1/8/pubmed PY - 2005/3/23/medline PY - 2004/1/8/entrez SP - 447 EP - 61 JF - Human molecular genetics JO - Hum. Mol. Genet. VL - 13 IS - 4 N2 - The relationships between MC1R gene variants and red hair, skin reflectance, degree of freckling and nevus count were investigated in 2331 adolescent twins, their sibs and parents in 645 twin families. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. Of nine MC1R variant alleles assayed, four common alleles were strongly associated with red hair and fair skin (Asp84Glu, Arg151Cys, Arg160Trp and Asp294His), with a further three alleles having low penetrance (Val60Leu, Val92Met and Arg163Gln). These variants were separately combined for the purposes of this analysis and designated as strong 'R' (OR=63.3; 95% CI 31.9-139.6) and weak 'r ' (OR=5.1; 95% CI 2.5-11.3) red hair alleles. Red-haired individuals are predominantly seen in the R/R and R/r groups with 67.1 and 10.8%, respectively. To assess the interaction of the brown eye color gene OCA2 on the phenotypic effects of variant MC1R alleles we included eye color as a covariate, and also genotyped two OCA2 SNPs (Arg305Trp and Arg419Gln), which were confirmed as modifying eye color. MC1R genotype effects on constitutive skin color, freckling and mole count were modified by eye color, but not genotype for these two OCA2 SNPs. This is probably due to the association of these OCA2 SNPs with brown/green not blue eye color. Amongst individuals with a R/R genotype (but not R/r), those who also had brown eyes had a mole count twice that of those with blue eyes. This suggests that other OCA2 polymorphisms influence mole count and remain to be described. SN - 0964-6906 UR - https://www.unboundmedicine.com/medline/citation/14709592/Interactive_effects_of_MC1R_and_OCA2_on_melanoma_risk_phenotypes_ L2 - https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/ddh043 DB - PRIME DP - Unbound Medicine ER -