Plasma 25-Hydroxyvitamin D, Hormonal Contraceptive Use, and the Plasma Proteome in Caucasian, East Asian, and South Asian Young Adults

Vitamin D affects gene expression,
but its downstream effects on
the proteome are unclear. Hormonal contraceptives (HC), which affect
vitamin D metabolism and have widespread effects on the plasma proteome,
may confound the association between vitamin D and the proteome. We
determined whether HC use modified the association between 25-hydroxyvitamin
D (25D) and a panel of 54 high-abundance plasma proteins. Cross-sectional
analyses were conducted in healthy, nonsmoking female HC users (n = 216), female HC nonusers (n = 502),
and men (n = 301) from Toronto, Canada. Plasma 25D
was measured by HPLC–MS/MS, and proteins were measured by LC-multiple-reaction-monitoring
(MRM)-MS. The 54 proteins clustered into four distinct proteomic profiles.
A positive association was observed between Profile 1, containing
positive acute phase proteins, and 25D. In female HC users, a J-shaped
association existed between Profile 1 and 25D, but no associations
existed in female HC nonusers and men. Twelve proteins were individually
associated with 25D in female HC users, but only two were associated
with 25D in female HC nonusers and no associations were observed in
men. After accounting for hormone dose, only three proteins were associated
with 25D. In summary, HC use is an important confounder of the association
between circulating 25D and numerous plasma proteins.