HLA-DRB1 and month of birth in multiple sclerosis.
BACKGROUND
Multiple sclerosis (MS) displays a month-of-birth effect, with an excess of individuals being born in the spring and a deficit in the winter. This effect was shown to be more pronounced in familial cases of MS. In the present study, we investigated whether this month-of-birth association has any relation to the principal MS susceptibility gene, HLA-DRB1.


METHODS
A total of 4,834 patients with MS, 4,056 controls, and 659 unaffected siblings from Canada, Sweden, and Norway were genotyped for the HLA-DRB1 gene. Month of birth was compared for patients, controls, and unaffected siblings with and without the MS risk allele HLA-DRB1*15.


RESULTS
Significantly fewer patients with MS carrying the HLA-DRB1*15 risk allele were born in November compared with patients not carrying this allele (p = 0.02). Additionally, patients with MS carrying HLA-DRB1*15 had a higher number of April births compared with patients with MS not carrying HLA-DRB1*15 (p = 0.004). These differences were not present in controls or unaffected siblings.


CONCLUSIONS
Month of birth, HLA-DRB1 genotype, and risk of multiple sclerosis are associated. The interaction of a seasonal risk factor with loci at or near HLA-DRB1 during gestation or shortly after birth is implicated.
Ramagopalan
S V
SV
Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford, UK.
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Byrnes
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Giovannoni
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Hintzen
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Sundqvist
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Kockum
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Smestad
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Harbo
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Padyukov
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Alfredsson
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Olsson
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Sadovnick
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Ebers
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D000483:Alleles; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D036801:Parturition; D018570:Risk Assessment; D012307:Risk Factors; D012621:Seasons
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains