Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis - PubMed (original) (raw)

Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis

Sarah-Michelle Orton et al. Am J Clin Nutr. 2008 Aug.

Abstract

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.

Objectives: 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)].

Design: 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.

Conclusion: The findings indicate important genetic influences on regulation of seasonal circulating 25(OH)D concentrations in MS twins.

PubMed Disclaimer

Figures

FIGURE 1.

FIGURE 1.

Intraclass correlation of serum 25-hyrdroxy-vitaminD [25(OH)D] concentration (in nmol/L) in monozygotic (MZ) and dizygotic (DZ) twin pairs. The Pearson correlation coefficients were r = 0.71 (P < 0.001) and r = 0.32 (P = 0.014) for MZ and DZ twins, respectively. The difference between the 2 correlation values was significant (P < 0.006). The dashed lines represent the theoretical axis for full correlation (r = 1) of 25(OH)D concentrations within each twin pair.

Similar articles

Cited by

References

    1. Peltonen L. Old suspects found guilty–the first genome profile of multiple sclerosis. N Engl J Med 2007;357:927–9. - PubMed
    1. Ebers GC, Sadovnick AD, Risch NJ. A genetic basis for familial aggregation in multiple sclerosis. Canadian Collaborative Study Group. Nature 1995;377:150–1. - PubMed
    1. Ebers GC, Sadovnick AD, Dyment DA, Yee IM, Willer CJ, Risch N. Parent-of-origin effect in multiple sclerosis: observations in half-siblings. Lancet 2004;363:1773–4. - PubMed
    1. Orton SM, Herrera BM, Yee IM, et al. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol 2006;5:932–6. - PubMed
    1. Dyment DA, Yee IM, Ebers GC, Sadovnick AD. Multiple sclerosis in stepsiblings: recurrence risk and ascertainment. J Neurol Neurosurg Psychiatry 2006;77:258–9. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources