Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis.
BACKGROUND
Multiple sclerosis (MS) risk is determined by both genes and environment. One of the most striking features of MS is its geographic distribution, particularly the pattern of high MS frequency in areas with low sunlight exposure, the main inducer of vitamin D synthesis. Recent epidemiologic, experimental, and clinical evidence support an effect for low environmental supplies of vitamin D in mediating an increased susceptibility to MS.


OBJECTIVE
We 1) examined the association of serum 25-hydroxy-vitaminD [25(OH)D] concentrations and MS status and 2) assessed the genetic contribution to serum 25(OH)D concentrations and tested for its association with genetic variants in 2 candidate genes [vitamin D receptor and 1-alpha-hydroxylase (CYP27B1)].


METHODS
We used a twin study approach, comprising adult pairs identified from the longitudinal population-based Canadian Collaborative Project on Genetic Susceptibility to MS. Monozygotic (MZ; n = 40) and dizygotic (DZ; n = 59) pairs, both concordant and discordant for MS, were studied. End-of-winter serum 25(OH)D concentrations were measured by radioimmunoassay, and genotypes were assessed by single nucleotide polymorphism (SNP) assay.


RESULTS
Serum concentrations of 25(OH)D were highly correlated in MS-concordant pairs (r = 0.83, P < 0.001), but they were not significantly associated with having the disease (P = 0.4) when analyzed by logistic regression. Intraclass correlation for 25(OH)D concentration was significantly greater in MZ pairs (MZ, r: 0.71 > DZ r: 0.32, P = 0.006). Significant associations of 2 CYP27B1 SNP variants and 25(OH)D concentrations were observed.


CONCLUSIONS
The findings indicate important genetic influences on regulation of seasonal circulating 25(OH)D concentrations in MS twins.
Orton
Sarah-Michelle
SM
Wellcome Trust Centre for Human Genetics and Department of Clinical Neurology, University of Oxford; Oxford, United Kingdom.
Morris
Andrew P
AP
Herrera
Blanca M
BM
Ramagopalan
Sreeram V
SV
Lincoln
Matthew R
MR
Chao
Michael J
MJ
Vieth
Reinhold
R
Sadovnick
A Dessa
AD
Ebers
George C
GC
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D000328:Adult; D000368:Aged; D004200:Diseases in Twins; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D009752:Nutritional Status; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D012621:Seasons; D013472:Sunlight; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D014807:Vitamin D / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000097:blood*
D018167:Receptors, Calcitriol; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase