Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
14709592
TITLE
Interactive effects of MC1R and OCA2 on melanoma risk phenotypes.
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.
DATE PUBLISHED
2004 Feb 15
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2004/01/08 05:00
medline 2005/03/23 09:00
aheadofprint 2004/00/06
entrez 2004/01/08 05:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Duffy DL Duffy David L DL Queensland Insititute of Medical Research, Brisbane, Australia.
Box NF Box Neil F NF
Chen W Chen Wei W
Palmer JS Palmer James S JS
Montgomery GW Montgomery Grant W GW
James MR James Michael R MR
Hayward NK Hayward Nicholas K NK
Martin NG Martin Nicholas G NG
Sturm RA Sturm Richard A RA
INVESTIGATORS
JOURNAL
VOLUME: 13
ISSUE: 4
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2004
MONTH: Feb
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0964-6906
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
CA88363 NCI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Alleles
Eye Color genetics
Genetic Predisposition to Disease genetics
Genetic Variation genetics
Hair Color genetics
Humans genetics
Membrane Transport Proteins genetics
Mutation genetics
Phenotype genetics
Receptor, Melanocortin, Type 1 genetics
Skin Pigmentation genetics
Twins genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Membrane Transport Proteins
0 OCA2 protein, human
0 Receptor, Melanocortin, Type 1
OTHER ID's