Vitamin D receptor gene haplotype is associated with body height and bone size.
BACKGROUND
Adult stature is a complex genetic trait. The vitamin D endocrine system has pleiotropic effects on several physiological processes, especially on skeletal metabolism. We recently identified promoter and 3'-untranslated region (UTR) haplotype alleles that influence vitamin D receptor (VDR) mRNA expression.


OBJECTIVE
We studied whether VDR gene variants contribute to the genetic variation in height.


METHODS
We studied VDR haplotype alleles and body height in two independent populations (n=7187). In a meta-analysis (n=14,157 from 27 studies and our current data), we evaluated the effect of the Bsm I polymorphism.


RESULTS
Haplotypes of the linkage disequilibrium block 3 and block 5 were associated with body height differences with evidence for additive effects in the Rotterdam Study (P=0.00002) and the Longitudinal Aging Study Amsterdam study (P=0.001). Height differences between the extreme genotypes were 1.4 and 2.7 cm, respectively. The relationship was independent of age, gender, presence of vertebral fractures, and age-related height loss. In the Rotterdam population, we found the combined genotype to be associated with decreased vertebral area (P=0.03) and femoral narrow neck width (P=0.002). In the meta-analysis, subjects with the "BB" genotype were 0.6 cm (95% confidence interval, 0.2-1.1 cm) taller than those with the "bb" genotype (P=0.006).


CONCLUSIONS
VDR gene variants are associated with differences in body height as evidenced by our study and by a meta-analysis. It remains for further studies to confirm whether the underlying mechanism of the association involves lower VDR expression in cells important for determining bone size.
Fang
Yue
Y
Genetic Laboratory, Room Ee575, Department of Internal Medicine, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
van Meurs
Joyce B J
JB
Rivadeneira
Fernando
F
van Schoor
Natasja M
NM
van Leeuwen
Johannes P T
JP
Lips
Paul
P
Pols
Huibert A P
HA
Uitterlinden
André G
AG
D000704:Analysis of Variance; D001827:Body Height / Q000235:genetics*; D001842:Bone and Bones / Q000033:anatomy & histology*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009929:Organ Size; D011110:Polymorphism, Genetic; D011187:Posture; D018167:Receptors, Calcitriol / Q000235:genetics*; D013997:Time Factors
D018167:Receptors, Calcitriol