FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 337:77-82 July 10, 1997 Number 2 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Bone mass is under strong genetic control, and recent studies in adults have suggested that allelic differences in the gene for the vitamin D receptor may account for inherited variability in bone mass. We studied the relations of the vitamin D–receptor genotype to skeletal development and variation in the size, volume, and density of bone in children.

Methods We identified three allelic variants of the vitamin D–receptor gene using the polymerase chain reaction and three restriction enzymes (ApaI, BsmI, and TaqI) in 100 normal prepubertal American girls of Mexican descent. We then determined the relations of the different vitamin D–receptor genotypes (AA, Aa, aa, BB, Bb, bb, TT, Tt, and tt) to the cross-sectional area, cortical area, and cortical bone density of the femoral shaft and the cross-sectional area and density of the lumbar vertebrae.

Results The vitamin D–receptor genotype was associated with femoral and vertebral bone density. Girls with aa and bb genotypes had 2 to 3 percent higher femoral bone density (P = 0.008 and P = 0.04, respectively) and 8 to 10 percent higher vertebral bone density (P = 0.01 and P = 0.03, respectively) than girls with AA and BB genotypes. There was no association between the cross-sectional area of the vertebrae or the cross-sectional or cortical area of the femur and the vitamin D–receptor genotype. The chronologic age, bone age, height, weight, body-surface area, and body-mass index did not differ significantly among girls with different vitamin D–receptor genotypes.

Conclusions Vitamin D–receptor gene alleles predict the density of femoral and vertebral bone in prepubertal American girls of Mexican descent.

Source Information

From the Departments of Radiology (J.S., M.L.L., V.G.) and Pediatrics (J.M.V.T., T.F.R.), Children's Hospital of Los Angeles and the University of Southern California; and the Department of Biostatistics, University of California, Los Angeles, School of Medicine (J.S.) — all in Los Angeles.

Address reprint requests to Dr. Gilsanz at the Radiology Dept., Children's Hospital of Los Angeles, 4650 Sunset Blvd., M.S. 81, Los Angeles, CA 90027.

Full Text of this Article

This article has been cited by other articles:

• Ranganathan, P. (2009). Genetics of bone loss in rheumatoid arthritis--role of vitamin D receptor polymorphisms. Rheumatology (Oxford) 48: 342-346 [Abstract] [Full Text]  
• Bezerra, F. F., Cabello, G. M. K., Mendonca, L. M. C., Donangelo, C. M. (2008). Bone Mass and Breast Milk Calcium Concentration Are Associated with Vitamin D Receptor Gene Polymorphisms in Adolescent Mothers. J. Nutr. 138: 277-281 [Abstract] [Full Text]  
• Wedren, S., Magnusson, C., Humphreys, K., Melhus, H., Kindmark, A., Stiger, F., Branting, M., Persson, I., Baron, J., Weiderpass, E. (2007). Associations between Androgen and Vitamin D Receptor Microsatellites and Postmenopausal Breast Cancer. Cancer Epidemiol. Biomarkers Prev. 16: 1775-1783 [Abstract] [Full Text]  
• Kishi, S., Cheng, C., French, D., Pei, D., Das, S., Cook, E. H., Hijiya, N., Rizzari, C., Rosner, G. L., Frudakis, T., Pui, C.-H., Evans, W. E., Relling, M. V. (2007). Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood 109: 4151-4157 [Abstract] [Full Text]  
• Fang, Y., van Meurs, J. B. J., Rivadeneira, F., van Schoor, N. M., van Leeuwen, J. P. T., Lips, P., Pols, H. A. P., Uitterlinden, A. G. (2007). Vitamin D Receptor Gene Haplotype Is Associated with Body Height and Bone Size. J. Clin. Endocrinol. Metab. 92: 1491-1501 [Abstract] [Full Text]  
• Gilsanz, V., Wren, T. (2007). Assessment of Bone Acquisition in Childhood and Adolescence. Pediatrics 119: S145-S149 [Abstract] [Full Text]  
• Dempfle, A., Wudy, S. A., Saar, K., Hagemann, S., Friedel, S., Scherag, A., Berthold, L. D., Alzen, G., Gortner, L., Blum, W. F., Hinney, A., Nurnberg, P., Schafer, H., Hebebrand, J. (2006). Evidence for involvement of the vitamin D receptor gene in idiopathic short stature via a genome-wide linkage study and subsequent association studies. Hum Mol Genet 15: 2772-2783 [Abstract] [Full Text]  
• d'Alesio, A., Garabedian, M., Sabatier, J. P., Guaydier-Souquieres, G., Marcelli, C., Lemacon, A., Walrant-Debray, O., Jehan, F. (2005). Two single-nucleotide polymorphisms in the human vitamin D receptor promoter change protein-DNA complex formation and are associated with height and vitamin D status in adolescent girls. Hum Mol Genet 14: 3539-3548 [Abstract] [Full Text]  
• Yahata, T., Quan, J., Tamura, N., Nagata, H., Kurabayashi, T., Tanaka, K. (2005). Association between single nucleotide polymorphisms of estrogen receptor {alpha} gene and efficacy of HRT on bone mineral density in post-menopausal Japanese women. Hum Reprod 20: 1860-1866 [Abstract] [Full Text]  
• Rocha, J. C. C., Cheng, C., Liu, W., Kishi, S., Das, S., Cook, E. H., Sandlund, J. T., Rubnitz, J., Ribeiro, R., Campana, D., Pui, C.-H., Evans, W. E., Relling, M. V. (2005). Pharmacogenetics of outcome in children with acute lymphoblastic leukemia. Blood 105: 4752-4758 [Abstract] [Full Text]  
• Davies, J H, Evans, B A J, Gregory, J W (2005). Bone mass acquisition in healthy children. Arch. Dis. Child. 90: 373-378 [Abstract] [Full Text]  
• Raby, B. A., Lazarus, R., Silverman, E. K., Lake, S., Lange, C., Wjst, M., Weiss, S. T. (2004). Association of Vitamin D Receptor Gene Polymorphisms with Childhood and Adult Asthma. Am. J. Respir. Crit. Care Med. 170: 1057-1065 [Abstract] [Full Text]  
• Poon, A. H., Laprise, C., Lemire, M., Montpetit, A., Sinnett, D., Schurr, E., Hudson, T. J. (2004). Association of Vitamin D Receptor Genetic Variants with Susceptibility to Asthma and Atopy. Am. J. Respir. Crit. Care Med. 170: 967-973 [Abstract] [Full Text]  
• Specker, B. (2004). Nutrition Influences Bone Development from Infancy through Toddler Years. J. Nutr. 134: 691S-695 [Abstract] [Full Text]  
• Matsushita, H., Kurabayashi, T., Tomita, M., Tanaka, K. (2004). Effects of vitamin D and estrogen receptor gene polymorphisms on the changes in lumbar bone mineral density with multiple pregnancies in Japanese women. Hum Reprod 19: 59-64 [Abstract] [Full Text]  
• Gong, M. N., Wei, Z., Xu, L.-L., Miller, D. P., Thompson, B. T., Christiani, D. C. (2004). Polymorphism in the Surfactant Protein-B Gene, Gender, and the Risk of Direct Pulmonary Injury and ARDS. Chest 125: 203-211 [Abstract] [Full Text]  
• Seeman, E. (2003). Invited Review: Pathogenesis of osteoporosis. J. Appl. Physiol. 95: 2142-2151 [Abstract] [Full Text]  
• Palomba, S., Numis, F. G., Mossetti, G., Rendina, D., Vuotto, P., Russo, T., Zullo, F., Nappi, C., Nunziata, V. (2003). Raloxifene administration in post-menopausal women with osteoporosis: effect of different BsmI vitamin D receptor genotypes. Hum Reprod 18: 192-198 [Abstract] [Full Text]  
• Tortolani, P. J., McCarthy, E. F., Sponseller, P. D. (2002). Bone Mineral Density Deficiency in Children. J Am Acad Orthop Surg 10: 57-66 [Abstract] [Full Text]  
• Eisman, J. A. (2001). Pharmacogenetics of the Vitamin D Receptor and Osteoporosis. Drug Metab. Dispos. 29: 505-512 [Abstract] [Full Text]  
• Soyka, L. A., Fairfield, W. P., Klibanski, A. (2000). Hormonal Determinants and Disorders of Peak Bone Mass in Children. J. Clin. Endocrinol. Metab. 85: 3951-3963 [Full Text]  
• Luiza Loro, M., Sayre, J., Roe, T. F., Goran, M. I., Kaufman, F. R., Gilsanz, V. (2000). Early Identification of Children Predisposed to Low Peak Bone Mass and Osteoporosis Later in Life. J. Clin. Endocrinol. Metab. 85: 3908-3918 [Abstract] [Full Text]  
• Mattano, L. A. Jr, Sather, H. N., Trigg, M. E., Nachman, J. B. (2000). Osteonecrosis as a Complication of Treating Acute Lymphoblastic Leukemia in Children: A Report From the Children's Cancer Group. JCO 18: 3262-3272 [Abstract] [Full Text]  
• Becherini, L., Gennari, L., Masi, L., Mansani, R., Massart, F., Morelli, A., Falchetti, A., Gonnelli, S., Fiorelli, G., Tanini, A., Brandi, M. L. (2000). Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor {alpha} gene and their relationship to bone mass variation in postmenopausal Italian women. Hum Mol Genet 9: 2043-2050 [Abstract] [Full Text]  
• Nelson, D A, Vande Vord, P J, Wooley, P H (2000). Polymorphism in the vitamin D receptor gene and bone mass in African-American and white mothers and children: a preliminary report. Ann Rheum Dis 59: 626-630 [Abstract] [Full Text]  
• Lorentzon, M., Lorentzon, R., Nordström, P. (2000). 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. J. Clin. Endocrinol. Metab. 85: 1666-1671 [Abstract] [Full Text]  
• Habuchi, T., Suzuki, T., Sasaki, R., Wang, L., Sato, K., Satoh, S., Akao, T., Tsuchiya, N., Shimoda, N., Wada, Y., Koizumi, A., Chihara, J., Ogawa, O., Kato, T. (2000). Association of Vitamin D Receptor Gene Polymorphism with Prostate Cancer and Benign Prostatic Hyperplasia in a Japanese Population. Cancer Res. 60: 305-308 [Abstract] [Full Text]  
• Eisman, J. A. (1999). Genetics of Osteoporosis. Endocr. Rev. 20: 788-804 [Abstract] [Full Text]  
• (1999). The Effects of Anorexia Nervosa on Bone Metabolism in Female Adolescents. J. Clin. Endocrinol. Metab. 84: 4489-4496 [Abstract] [Full Text]  
• (1999). Vitamin D Supplementation during Infancy Is Associated with Higher Bone Mineral Mass in Prepubertal Girls. J. Clin. Endocrinol. Metab. 84: 4541-4544 [Abstract] [Full Text]  
• Guardiola, J., Xiol, X., Sallie, R., Nolla, J. M., Roig-Escofet, D., Jaurrieta, E., Casais, L. (1999). Influence of the Vitamin D Receptor Gene Polymorphism on Bone Loss in Men after Liver Transplantation. ANN INTERN MED 131: 752-755 [Abstract] [Full Text]  
• Miller, K. K., Klibanski, A. (1999). Amenorrheic Bone Loss. J. Clin. Endocrinol. Metab. 84: 1775-1783 [Full Text]  
• Ferrari, S., Manen, D., Bonjour, J.-P., Slosman, D., Rizzoli, R. (1999). Bone Mineral Mass and Calcium and Phosphate Metabolism in Young Men: Relationships with Vitamin D Receptor Allelic Polymorphisms. J. Clin. Endocrinol. Metab. 84: 2043-2048 [Abstract] [Full Text]  
• Sainz, J., Van Tornout, J. M., Sayre, J., Kaufman, F., Gilsanz, V. (1999). Association of Collagen Type 1 {alpha}1 Gene Polymorphism with Bone Density in Early Childhood. J. Clin. Endocrinol. Metab. 84: 853-855 [Abstract] [Full Text]  
• Abrams, S. A., Copeland, K. C., Gunn, S. K., Stuff, J. E., Clarke, L. L., Ellis, K. J. (1999). Calcium Absorption and Kinetics Are Similar in 7- and 8-Year-Old Mexican-American and Caucasian Girls Despite Hormonal Differences. J. Nutr. 129: 666-671 [Abstract] [Full Text]  
• Tao, C., Yu, T., Garnett, S., Briody, J., Knight, J., Woodhead, H., Cowell;, C. T, MUGHAL, Z. (1998). Vitamin D receptor alleles predict growth and bone density in girls • Commentary. Arch. Dis. Child. 79: 488-494 [Abstract] [Full Text]  
• Suarez, F., Rossignol, C., Garabédian, M. (1998). Interactive Effect of Estradiol and Vitamin D Receptor Gene Polymorphisms as a Possible Determinant of Growth in Male and Female Infants. J. Clin. Endocrinol. Metab. 83: 3563-3568 [Abstract] [Full Text]  
• Riggs, B. L. (1997). Vitamin D-Receptor Genotypes and Bone Density. NEJM 337: 125-126 [Full Text]