The median (interquartile range) unadjusted 25-hydroxyvitamin D level was 29.7 (19.7–46.2) nmol/L in the MS group and 36.6 (24.0–51.9) nmol/L in controls (p
= 0.0001) (). Seventy-seven percent of the MS group and 71% of controls had 25-hydroxyvitamin D levels in a range commonly considered to be vitamin D deficient (<50 nmol/L or <20 ng/mL), and 94% of the MS group and 93% of controls had levels in a range commonly considered to be vitamin D insufficient (<75 nmol/L or <30 ng/mL).16
The distribution of 25-hydroxyvitamin D levels was modestly left skewed with a long right tail. Differences in the seasonal variation of unadjusted 25-hydroxyvitamin D levels were examined in the control population across 3 latitude bands (<37 degrees, ≥37 to <41 degrees, and ≥41 degrees) (table e-1). Season was highly associated with vitamin D status across all latitude bands, but differences in amounts of seasonal variation were not significant between latitude bands (analysis of variance, p = 0.11); similar results were obtained using the square root of unadjusted 25-hydroxyvitamin D, which was normally distributed (p = 0.08). Because season was highly correlated with vitamin D status and there were no significant differences in seasonal variation between latitude bands, we elected to use deseasonalized vitamin D levels for subsequent analysis. Entirely separate analyses by latitude band were not possible based on sample size. A parallel analysis using unadjusted 25-hydroxyvitamin D values is also reported.
Compared with the control group, the MS group was slightly younger, more likely to be female, tended to live in higher latitudes, and had a lower average monthly UV index at the time of blood draw (). Proportion of European genetic ancestry was similar between the MS group and controls.
Deseasonalized 25-hydroxyvitamin D was slightly but significantly lower in the MS group compared to controls (p = 0.001) ( and ), as were unadjusted 25-hydroxyvitamin D levels. On multivariable analysis (), lower deseasonalized 25-hydroxyvitamin D remained associated with MS status after adjustment for age, sex, and HLA-DRB1*15 (which was highly associated with MS status). Differences in latitude between groups accounted for much of this apparent association. Similar results were observed using unadjusted 25-hydroxyvitamin D levels and adjusting for UV index (table e-2).
A greater proportion of European genetic ancestry was positively correlated with 25-hydroxyvitamin D status in this African American dataset, an association that retained statistical significance even after adjusting for differences in latitude () or UV index (table e-3). The association between European genetic admixture and vitamin D status was also present in the control population alone (p = 0.012 univariate, p = 0.01 adjusting for latitude). As expected, UV index and latitude were highly correlated with 25-hydroxyvitamin D status. A possible interaction between MS status and proportion of European ancestry was examined for by adding a multiplicative term to the model and not found. Additional factors that were not predictive of vitamin D status were age, sex, HLA-DRB*15 status, and length of blood storage time.
Proportion of European genetic ancestry, a measure of genetic admixture, is positively correlated with vitamin D statusa
The median (interquartile range) MSSS of the MS group was 6.1 (4.8–8.1), indicating a high rate of ambulatory disability in this study sample. There was no association between MSSS and vitamin D status using linear regression. Per 10 nmol/L deseasonalized 25-hydroxyvitamin D, the β coefficient was −0.034, 95% confidence interval (CI) −0.15 to 0.08, p = 0.57. Per 10 nmol/L unadjusted 25-hydroxyvitamin D, the β coefficient was −0.034, 95% CI −0.15 to 0.08, p = 0.56. There was no association between low vs high MSSS (MSSS ≤6 vs MSSS >6) and vitamin D status using logistic regression for deseasonalized vitamin D (odds ratio [OR] 0.97, 95% CI 0.65 to 1.43, p = 0.86) or unadjusted 25-hydroxyvitamin D (OR 1.009, 95% CI 0.66 to 1.5, p = 0.97), adjusting for age and sex. There was also no association between MSSS and vitamin D status using ordinal logistic regression (categorizing by MSSS 0 to ≤2, >2 to ≤4, >4 to ≤6, >6 to ≤8, >8 to ≤10). Adjusting for HLA-DRB1*15 status and proportion of European genetic ancestry in the above regression models did not alter this result. There was no association between MSSS and age, HLA-DRB1*15 status, proportion of European genetic ancestry, or latitude (for deseasonalized) or UV index (for unadjusted 25-hydroxyvitamin D). There was no apparent association between EDSS and unadjusted or deseasonalized 25-hydroxyvitamin D.