Vitamin D receptor gene polymorphism is associated with birth height, growth to adolescence, and adult stature in healthy caucasian men: a cross-sectional and longitudinal study.

Vitamin D receptor (VDR) polymorphism has been associated with bone mineral density (BMD), but recent data indicate association to parameters of body constitution and growth. We investigated VDR gene polymorphism, defined by BsmI and TaqI, in 90 healthy Caucasian males and any relation with parameters of body constitution at birth, and to parameters of body constitution, BMD and bone area, at age 16.9 +/- 0.3 yr (mean +/- SD) and at age 19.2 +/- 0.7. Using PCR and the restriction enzyme BsmI and TaqI, the allelic variants BB, Bb, and bb, and TT, Tt, and tt were identified. Height (cm) and weight (kg) were measured using standardized equipment, and BMD of the total body, lumbar spine, and femoral neck, and bone area (cm2) of the total body, humerus, femur was measured using dual-energy x-ray absorptiometry. BsmI and TaqI genotypes were related in 89 of the 90 cases; hence, the same associations were found for both genotypes. Boys with the BB genotype were shorter at birth (P = 0.01) and grew less from birth to age 16.9 +/- 0.3 (P = 0.01) than their Bb and bb counterparts. Both during puberty (age 16.9 +/- 0.3) and after puberty (age 19.3 +/- 0.7), the BB boys were shorter (P = 0.005-0.008) and had lower bone area of the humerus, femur, and total body (P < 0.05) than the Bb and bb boys. The allelic variants were not related to BMD at any site. A prediction model including parental height, birth height, birth weight, and VDR alleles could predict up to 39% of the total variation in adult height in our population. The VDR allelic variants alone contributed to 8% of the total variation.

[1]  Ames,et al.  Vitamin D-receptor gene polymorphisms and bone density in prepubertal American girls of Mexican descent. , 1997, The New England journal of medicine.

[2]  P. Jansson,et al.  Lactate and glycerol release from subcutaneous adipose tissue in black and white lean men. , 1999, The Journal of clinical endocrinology and metabolism.

[3]  R. Rizzoli,et al.  Bone mineral mass and calcium and phosphate metabolism in young men: relationships with vitamin D receptor allelic polymorphisms. , 1999, The Journal of clinical endocrinology and metabolism.

[4]  S. Abrams,et al.  Vitamin D Receptor Gene Fok1 Polymorphism Predicts Calcium Absorption and Bone Mineral Density in Children , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  K. Rothman,et al.  Birth weight and length as predictors for adult height. , 1999, American journal of epidemiology.

[6]  M. Minagawa,et al.  Difference in Height Associated with a Translation Start Site Polymorphism in the Vitamin D Receptor Gene1 , 1998, Pediatric Research.

[7]  Zhong-Cheng Luo,et al.  Target Height as Predicted by Parental Heights in a Population-Based Study , 1998, Pediatric Research.

[8]  R. Baron,et al.  Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. , 1998, Endocrinology.

[9]  R. Rizzoli,et al.  Vitamin D Receptor Gene Start Codon Polymorphisms (FokI) and Bone Mineral Density: Interaction with Age, Dietary Calcium, and 3′‐End Region Polymorphisms , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[10]  K. Lau,et al.  Vitamin D receptor gene polymorphisms and peak bone mass in southern Chinese women. , 1998, Bone.

[11]  M. Haussler,et al.  The Nuclear Vitamin D Receptor: Biological and Molecular Regulatory Properties Revealed , 1998, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[12]  R. Wood,et al.  The genetics of osteoporosis: vitamin D receptor polymorphisms. , 1998, Annual review of nutrition.

[13]  M. Brandi,et al.  Vitamin D Receptor Genotypes and Intestinal Calcium Absorption in Postmenopausal Women , 1997, Calcified Tissue International.

[14]  R. Baron,et al.  Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Garabédian,et al.  Association between vitamin D receptor gene polymorphism and sex-dependent growth during the first two years of life. , 1997, The Journal of clinical endocrinology and metabolism.

[16]  H. DeLuca,et al.  Effect of Vitamin D Receptor Genotypes on Calcium Absorption, Duodenal Vitamin D Receptor Concentration, and Serum 1,25 Dihydroxyvitamin D Levels in Normal Women , 1997, Calcified Tissue International.

[17]  P. Roberson,et al.  Quantification of Vitamin D Receptor mRNA by Competitive Polymerase Chain Reaction in PBMC: Lack of Correspondence with Common Allelic Variants , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[18]  T. Spector,et al.  Polymorphisms of the Vitamin D Receptor, Infant Growth, and Adult Bone Mass , 1997, Calcified Tissue International.

[19]  J. Berg,et al.  Lack of relationship between vitamin D receptor genotype and forearm bone gain in healthy children, adolescents, and young adults. , 1997, The Journal of clinical endocrinology and metabolism.

[20]  G. Cooper,et al.  Are vitamin D receptor polymorphisms associated with bone mineral density? A meta‐analysis , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[21]  M. Horowitz,et al.  Vitamin D receptor genotypes are related to bone size and bone density in men , 1996, European journal of clinical investigation.

[22]  R. Bouillon,et al.  Structure-function relationships in the vitamin D endocrine system. , 1995, Endocrine reviews.

[23]  J. Eisman,et al.  Prediction of bone density from vitamin D receptor alleles , 1994, Nature.

[24]  E. Orwoll,et al.  Precision of dual‐energy x‐ray absorptiometry: Development of quality control rules and their application in longitudinal studies , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[25]  I. Vuori,et al.  Precision of dual-energy x-ray absorptiometry in determining bone mineral density and content of various skeletal sites. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[26]  R. Rizzoli,et al.  Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. , 1991, The Journal of clinical endocrinology and metabolism.

[27]  R. Renkawitz-Pohl,et al.  Intron and upstream sequences regulate expression of the Drosophila beta 3-tubulin gene in the visceral and somatic musculature, respectively. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[28]  B. Boyan,et al.  Effects of vitamin D metabolites on collagen production and cell proliferation of growth zone and resting zone cartilage cells in vitro , 1989, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[29]  S. Dekel,et al.  Healing of rachitic lesions in chicks by 24R,25‐dihydroxycholecalciferol administered locally into bone , 1987, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[30]  D. Howell,et al.  Effects of vitamin D metabolites on healing of low phosphate, vitamin D-deficient induced rickets in rats. , 1985, Bone.

[31]  O. Brooke,et al.  Intrauterine vitamin D nutrition and postnatal growth in Asian infants. , 1981, British medical journal.

[32]  A. Ornoy,et al.  24, 25-Dihydroxyvitamin D is a metabolite of vitamin D essential for bone formation , 1978, Nature.

[33]  M. Dumontier,et al.  Vitamin D and Cartilage. II. Biological Activity of 25-Hydroxycholecalciferol and 24,25- and 1,25-Dihydroxycholecalciferols on Cultured Growth Plate Chondrocytes* , 1978 .

[34]  D. A. Sholl,et al.  Growth at Adolescence , 1962 .