Vitamin D receptor Fok1 polymorphism influences response to vitamin D supplementation in postmenopausal African-American women

In this double-blind study of postmenopausal black women (n = 91), we hypothesized that vitamin D supplementation (1000 IU/day cholecalciferol) would prevent bone loss as compared to placebo, and furthermore that vitamin D receptor (VDR) polymorphisms might modify this response. Measurements of 25(OH)D, PTH, and bone turnover and bone mineral density (BMD) of the spine and hip were made at baseline, 3, 6, 12, and 24 months of the study. DNA was extracted from peripheral blood leukocytes and genotyping for the Fok1 polymorphism was performed by PCR-RFLP. Serum 25(OH)D increased 11 ng/ml with vitamin D supplementation (P < 0.001) and did not change in the placebo group, with no differences by genotype. There was greater PTH suppression with vitamin D as compared to placebo (both P < 0.02) but only in the FF group. Furthermore, in FF subjects, the slope of BMD change in the hip in response to vitamin D supplementation was significantly less than the slope of bone loss in the placebo group (all P < 0.001). However, there was no effect of vitamin D on BMD as compared to placebo in the Ff/ff group. Fok1 polymorphism of the vitamin D receptor gene may alter the response of African-American women to vitamin D supplementation.