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


CONCLUSIONS
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.
Dwyer
T
T
Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville Victoria 3052, Australia. terry.dwyer@mcri.edu.au
van der Mei
I
I
Ponsonby
A-L
AL
Taylor
B V
BV
Stankovich
J
J
McKay
J D
JD
Thomson
R J
RJ
Polanowski
A M
AM
Dickinson
J L
JL
D000328:Adult; D016022:Case-Control Studies; D004185:Disability Evaluation; D004781:Environmental Exposure; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006200:Hair Color / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D018570:Risk Assessment; D013472:Sunlight; D013648:Tasmania / Q000453:epidemiology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D044102:Receptor, Melanocortin, Type 1; D014807:Vitamin D; C104450:25-hydroxyvitamin D