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

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posted on 2023-05-16, 22:03 authored by Terry DwyerTerry Dwyer, Ingrid van der MeiIngrid van der Mei, Ponsonby, AL, Bruce TaylorBruce Taylor, Jim Stankovich, McKay, JD, Russell Thomson, Polanowski, AM, Joanne DickinsonJoanne Dickinson
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.

History

Publication title

Neurology

Volume

71

Issue

8

Pagination

583-589

ISSN

0028-3878

Department/School

Menzies Institute for Medical Research

Publisher

Lippincott Williams & Wilkins

Place of publication

USA

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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