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Melanocortin 1 receptor genotype, past environmental sun exposure, and risk of multiple sclerosis.

Abstract

OBJECTIVE

Low past sun exposure, fair skin type, and polymorphisms of the MC1R gene have been associated with multiple sclerosis (MS) risk. We aimed to investigate the interplay between melanocortin 1 receptor gene variants, red hair/fair skin phenotype, and past environmental sun exposure in MS.

METHODS

Population-based case-control study in Tasmania, Australia, involving 136 cases with MS and 272 controls randomly drawn from the community and matched on sex and year of birth. Measures included past sun exposure by calendar and questionnaire, spectrophotometric skin type, and MC1R genotype, with any MC1R Arg151Cys, Arg160Trp, or Asp294His alleles present denoted as red hair color (RHC) variant.

RESULTS

The association between RHC variant genotype and MS was more evident for women (odds ratio 2.02 [1.15-3.54]) than for men (odds ratio 0.65 [0.27-1.57]) (difference in effect, p = 0.03). The RHC variant genotype was associated with behavioral sun avoidance. In addition, increasing summer sun exposure at ages 6 through 10 years was associated with reduced MS risk among those with no RHC variant (p = 0.03), but not among those with RHC variant genotype (p = 0.15; difference in effect, p = 0.02). Similar findings were evident for other past sun exposure measures and when the sample was restricted to women only.

CONCLUSION

The interplay between red hair color variant genotype, red hair/fair skin phenotype, and multiple sclerosis (MS) is complex. The modification of past sun exposure by MC1R genotype provides further support that ultraviolet radiation or derivatives such as vitamin D may be causally related to a reduced MS risk.

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  • Authors+Show Affiliations

    ,

    Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville Victoria 3052, Australia. terry.dwyer@mcri.edu.au

    , , , , , , ,

    Source

    Neurology 71:8 2008 Aug 19 pg 583-9

    MeSH

    Adult
    Case-Control Studies
    Disability Evaluation
    Environmental Exposure
    Epstein-Barr Virus Infections
    Female
    Gene Frequency
    Genetic Variation
    Genotype
    HLA-DR Antigens
    HLA-DRB1 Chains
    Hair Color
    Humans
    Male
    Middle Aged
    Multiple Sclerosis
    Phenotype
    Polymorphism, Single Nucleotide
    Receptor, Melanocortin, Type 1
    Risk Assessment
    Sunlight
    Tasmania
    Vitamin D

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    18711112

    Citation

    Dwyer, T, et al. "Melanocortin 1 Receptor Genotype, Past Environmental Sun Exposure, and Risk of Multiple Sclerosis." Neurology, vol. 71, no. 8, 2008, pp. 583-9.
    Dwyer T, van der Mei I, Ponsonby AL, et al. Melanocortin 1 receptor genotype, past environmental sun exposure, and risk of multiple sclerosis. Neurology. 2008;71(8):583-9.
    Dwyer, T., van der Mei, I., Ponsonby, A. L., Taylor, B. V., Stankovich, J., McKay, J. D., ... Dickinson, J. L. (2008). Melanocortin 1 receptor genotype, past environmental sun exposure, and risk of multiple sclerosis. Neurology, 71(8), pp. 583-9. doi:10.1212/01.wnl.0000323928.57408.93.
    Dwyer T, et al. Melanocortin 1 Receptor Genotype, Past Environmental Sun Exposure, and Risk of Multiple Sclerosis. Neurology. 2008 Aug 19;71(8):583-9. PubMed PMID: 18711112.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Melanocortin 1 receptor genotype, past environmental sun exposure, and risk of multiple sclerosis. AU - Dwyer,T, AU - van der Mei,I, AU - Ponsonby,A-L, AU - Taylor,B V, AU - Stankovich,J, AU - McKay,J D, AU - Thomson,R J, AU - Polanowski,A M, AU - Dickinson,J L, PY - 2008/8/20/pubmed PY - 2008/10/8/medline PY - 2008/8/20/entrez SP - 583 EP - 9 JF - Neurology JO - Neurology VL - 71 IS - 8 N2 - OBJECTIVE: Low past sun exposure, fair skin type, and polymorphisms of the MC1R gene have been associated with multiple sclerosis (MS) risk. We aimed to investigate the interplay between melanocortin 1 receptor gene variants, red hair/fair skin phenotype, and past environmental sun exposure in MS. METHODS: Population-based case-control study in Tasmania, Australia, involving 136 cases with MS and 272 controls randomly drawn from the community and matched on sex and year of birth. Measures included past sun exposure by calendar and questionnaire, spectrophotometric skin type, and MC1R genotype, with any MC1R Arg151Cys, Arg160Trp, or Asp294His alleles present denoted as red hair color (RHC) variant. RESULTS: The association between RHC variant genotype and MS was more evident for women (odds ratio 2.02 [1.15-3.54]) than for men (odds ratio 0.65 [0.27-1.57]) (difference in effect, p = 0.03). The RHC variant genotype was associated with behavioral sun avoidance. In addition, increasing summer sun exposure at ages 6 through 10 years was associated with reduced MS risk among those with no RHC variant (p = 0.03), but not among those with RHC variant genotype (p = 0.15; difference in effect, p = 0.02). Similar findings were evident for other past sun exposure measures and when the sample was restricted to women only. CONCLUSION: The interplay between red hair color variant genotype, red hair/fair skin phenotype, and multiple sclerosis (MS) is complex. The modification of past sun exposure by MC1R genotype provides further support that ultraviolet radiation or derivatives such as vitamin D may be causally related to a reduced MS risk. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/18711112/Melanocortin_1_receptor_genotype_past_environmental_sun_exposure_and_risk_of_multiple_sclerosis_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=18711112 DB - PRIME DP - Unbound Medicine ER -