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Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral density: interaction with age, dietary calcium, and 3'-end region polymorphisms.
J Bone Miner Res. 1998 Jun; 13(6):925-30.JB

Abstract

Osteoporosis is a polygenic disease, whose determining loci have not yet been identified. Vitamin D receptor (VDR) gene polymorphisms in the 3'-end region (as determined by the enzymes BsmI and ApaI) have been inconsistently associated with bone mineral mass. More recently, VDR start codon polymorphisms (as determined by the enzyme FokI) have been found to be related to adult bone mineral density (BMD) in pre- and postmenopausal American women. We investigated the association between BMD and FokI genotypes in premenopausal European-Caucasian women as well as in prepubertal girls from the same genetic background and examined the interaction with VDR 3'-end region polymorphisms and with dietary calcium intake. Areal BMD (g/cm2) was measured by dual-energy X-ray absorptiometry at the level of the lumbar spine, femoral neck, and femoral shaft in 177 healthy premenopausal women (age range, 18.7-56.0 years) as well as in 155 prepubertal girls (age range, 6.6-11.4 years). Genotyping for FokI, BsmI, and ApaI VDR polymorphisms was performed using polymerase chain reaction methods. FokI genotype-dietary calcium interaction was cross-sectionally analyzed in all subjects and longitudinally in 103 prepubertal girls enrolled in a calcium intervention trial. The prevalence of FokI VDR gene polymorphisms in this cohort was 15% for ff, 50% for Ff, and 35% for FF. In the whole cohort of premenopausal women or prepubertal girls, no significant association was found between FokI VDR gene polymorphisms and BMD, even adjusted for age (Z score), weight, height, and calcium intake. Further analysis of FokI VDR gene polymorphisms and dietary calcium intake suggested a possible interaction in BMD determination, since a trend for an association with FokI genotypes was more evident at high than low calcium intake in both cross-sectional and longitudinal studies. Furthermore, cross-genotyping FokI and either BsmI or ApaI VDR polymorphisms suggested that the ff genotype was associated with a significantly lower lumbar spine BMD in bb and aa prepubertal girls. FokI VDR gene polymorphisms were not significantly associated with BMD in healthy European-Caucasian females. However, cross-genotyping of the VDR 3'-end and start codon polymorphic regions may provide a further insight into the complex determination of BMD.

Authors+Show Affiliations

WHO Center for Osteoporosis and Bone Diseases, Department of Internal Medicine, University Hospital, Geneva, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9626623

Citation

Ferrari, S, et al. "Vitamin D Receptor Gene Start Codon Polymorphisms (FokI) and Bone Mineral Density: Interaction With Age, Dietary Calcium, and 3'-end Region Polymorphisms." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 13, no. 6, 1998, pp. 925-30.
Ferrari S, Rizzoli R, Manen D, et al. Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral density: interaction with age, dietary calcium, and 3'-end region polymorphisms. J Bone Miner Res. 1998;13(6):925-30.
Ferrari, S., Rizzoli, R., Manen, D., Slosman, D., & Bonjour, J. P. (1998). Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral density: interaction with age, dietary calcium, and 3'-end region polymorphisms. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 13(6), 925-30.
Ferrari S, et al. Vitamin D Receptor Gene Start Codon Polymorphisms (FokI) and Bone Mineral Density: Interaction With Age, Dietary Calcium, and 3'-end Region Polymorphisms. J Bone Miner Res. 1998;13(6):925-30. PubMed PMID: 9626623.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral density: interaction with age, dietary calcium, and 3'-end region polymorphisms. AU - Ferrari,S, AU - Rizzoli,R, AU - Manen,D, AU - Slosman,D, AU - Bonjour,J P, PY - 1998/6/17/pubmed PY - 1998/6/17/medline PY - 1998/6/17/entrez SP - 925 EP - 30 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J. Bone Miner. Res. VL - 13 IS - 6 N2 - Osteoporosis is a polygenic disease, whose determining loci have not yet been identified. Vitamin D receptor (VDR) gene polymorphisms in the 3'-end region (as determined by the enzymes BsmI and ApaI) have been inconsistently associated with bone mineral mass. More recently, VDR start codon polymorphisms (as determined by the enzyme FokI) have been found to be related to adult bone mineral density (BMD) in pre- and postmenopausal American women. We investigated the association between BMD and FokI genotypes in premenopausal European-Caucasian women as well as in prepubertal girls from the same genetic background and examined the interaction with VDR 3'-end region polymorphisms and with dietary calcium intake. Areal BMD (g/cm2) was measured by dual-energy X-ray absorptiometry at the level of the lumbar spine, femoral neck, and femoral shaft in 177 healthy premenopausal women (age range, 18.7-56.0 years) as well as in 155 prepubertal girls (age range, 6.6-11.4 years). Genotyping for FokI, BsmI, and ApaI VDR polymorphisms was performed using polymerase chain reaction methods. FokI genotype-dietary calcium interaction was cross-sectionally analyzed in all subjects and longitudinally in 103 prepubertal girls enrolled in a calcium intervention trial. The prevalence of FokI VDR gene polymorphisms in this cohort was 15% for ff, 50% for Ff, and 35% for FF. In the whole cohort of premenopausal women or prepubertal girls, no significant association was found between FokI VDR gene polymorphisms and BMD, even adjusted for age (Z score), weight, height, and calcium intake. Further analysis of FokI VDR gene polymorphisms and dietary calcium intake suggested a possible interaction in BMD determination, since a trend for an association with FokI genotypes was more evident at high than low calcium intake in both cross-sectional and longitudinal studies. Furthermore, cross-genotyping FokI and either BsmI or ApaI VDR polymorphisms suggested that the ff genotype was associated with a significantly lower lumbar spine BMD in bb and aa prepubertal girls. FokI VDR gene polymorphisms were not significantly associated with BMD in healthy European-Caucasian females. However, cross-genotyping of the VDR 3'-end and start codon polymorphic regions may provide a further insight into the complex determination of BMD. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/9626623/Vitamin_D_receptor_gene_start_codon_polymorphisms__FokI__and_bone_mineral_density:_interaction_with_age_dietary_calcium_and_3'_end_region_polymorphisms_ L2 - https://doi.org/10.1359/jbmr.1998.13.6.925 DB - PRIME DP - Unbound Medicine ER -