Vitamin D receptor Fok1 polymorphisms affect calcium absorption, kinetics, and bone mineralization rates during puberty.
Few studies of the VDR polymorphisms have looked at calcium metabolism or long-term effects. We measured bone mineralization and calcium metabolic parameters longitudinally in a group of 99 adolescents. We found a significant relationship between calcium absorption and skeletal calcium accretion and the Fok1, but not other VDR or related, genetic polymorphisms. It seems that the Fok1 polymorphism directly affects bone mineralization during pubertal growth through an effect on calcium absorption.


BACKGROUND
There are few data regarding the relationship between genetic markers for low bone mass and changes in calcium metabolism in childhood or adolescence. We sought to identify the effects of polymorphisms of the vitamin D receptor (VDR) on calcium and bone mineral metabolism in a longitudinal study of pubertal adolescents.


METHODS
Adolescents (n = 99) received comprehensive stable isotope studies of calcium absorption, bone calcium kinetics, and bone mineralization. Studies were repeated 12 months later. Polymorphisms of putative genetic markers were determined and related to bone mineralization and calcium metabolic finding. Results were analyzed by ANOVA in which changes over time were determined using the initial value as a covariate.


RESULTS
Polymorphisms of the Fok1 gene of the VDR were significantly related to calcium absorption (p = 0.008) and whole body BMC (p = 0.03) and BMD (p = 0.006). The Fok1 effect on whole body BMD was significant for those with Ca intake >800 mg/day (p < 0.001), whereas for those with Ca intake < or = 800 mg/day, the Fok1 genotype did not have a significant effect on whole body BMD (p = 0.40). The Fok1 genotype was significantly related to the changes during the year in whole body calcium accretion, with the ff genotype having a 63 +/- 20 mg/day deficit compared with the FF genotype (p = 0.008).


CONCLUSIONS
The Fok1 polymorphism of the VDR receptor seems to directly affect bone mineral accretion during pubertal growth through an effect on calcium absorption. The relationship between different genetic polymorphisms and bone mineral metabolism may vary by life stage as well as diet.
Abrams
Steven A
SA
US Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Houston, Texas 77030, USA. sabrams@bcm.edu
Griffin
Ian J
IJ
Hawthorne
Keli M
KM
Chen
Zhensheng
Z
Gunn
Sheila K
SK
Wilde
Margaret
M
Darlington
Gretchen
G
Shypailo
Roman J
RJ
Ellis
Kenneth J
KJ
D000704:Analysis of Variance; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D002648:Child; D004032:Diet; D005260:Female; D005630:Fructans / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007118:Immunoassay; D007444:Inulin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D015675:Osteocalcin / Q000378:metabolism; D010919:Placebos; D011110:Polymorphism, Genetic; D011134:Polysaccharides / Q000494:pharmacology; D018167:Receptors, Calcitriol / Q000097:blood / Q000235:genetics* / Q000502:physiology*; D012984:Software; D013997:Time Factors; D014807:Vitamin D / Q000378:metabolism
D005630:Fructans; D010919:Placebos; D011134:Polysaccharides; D018167:Receptors, Calcitriol; D015675:Osteocalcin; D014807:Vitamin D; C008315:maltodextrin; D007444:Inulin; D002118:Calcium