Journal ArticleDOI
Birthweight, vitamin D receptor genotype and the programming of osteoporosis.
Elaine M. Dennison,Nigel K Arden,R W Keen,Holly E. Syddall,Ian N. M. Day,Tim D. Spector,Cyrus Cooper +6 more
TLDR
The results suggest that genetic influences on adult bone size and mineral density may be modified by undernutrition in utero.Abstract:
Studies of the association between polymorphisms of the gene for the vitamin D receptor (VDR) and adult bone mass have been inconsistent, pointing to the possibility that gene--environment interactions may vary in different populations. We have demonstrated previously an association between weight in infancy (a marker of the intrauterine and early post-natal environment) and each of adult bone mass and VDR genotype. We therefore sought to extend these observations in an elderly UK cohort and to investigate the possibility of an interaction between these genetic and early environmental markers of later osteoporosis risk. One hundred and sixty-five men and 126 women aged 61--73 years for whom birth records were available underwent bone mass measurements at baseline and follow-up 4 years later. Whole-blood samples were obtained, DNA extracted using standard techniques and polymorphisms in the VDR and collagen type I alpha 1 (Col IA1) genes identified. In the cohort as a whole, there were no significant associations between either birthweight or VDR genotype and bone mineral density (BMD) or bone loss rate at either site. However, the relationship between lumbar spine BMD and VDR genotype varied according to birthweight. Among individuals in the lowest third of birthweight, spine BMD was higher (P = 0.01) in individuals of genotype 'BB' after adjustment for age, sex and weight at baseline. In contrast, spine BMD was reduced (P = 0.04) in individuals of the same genotype who were in the highest third of the birthweight distribution. A significant (P = 0.02) statistical interaction was also found between VDR genotype and birthweight as determinants of BMD. Similar but slightly weaker associations were seen between lumbar spine bone mineral content (BMC) and VDR genotype in the lowest birthweight tertile. When examining the relationship between Col1A1 genotype and bone mass, lumbar spine BMC was higher in individuals of genotype 'Ss' or 'ss' in the lowest birthweight tertile (P = 0.02) after adjustment for age, sex and weight at baseline. These results suggest that genetic influences on adult bone size and mineral density may be modified by undernutrition in utero.read more
Citations
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Journal ArticleDOI
Effect of In Utero and Early-Life Conditions on Adult Health and Disease
TL;DR: Evidence from several disciplines is synthesized to support the contention that environmental factors acting during development should be accorded greater weight in models of disease causation.
Journal ArticleDOI
Living with the past: evolution, development, and patterns of disease
Peter D. Gluckman,Mark A. Hanson +1 more
TL;DR: Research in evolutionary biology, developmental biology, and animal and human physiology suggests that environmental processes influencing the propensity to disease in adulthood operate during the periconceptual, fetal, and infant phases of life.
Journal ArticleDOI
Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study
Muhammad Javaid,Sarah Crozier,Nicholas C. Harvey,Catharine R. Gale,Elaine M. Dennison,Barbara J. Boucher,Nigel K Arden,Keith M. Godfrey,Cyrus Cooper +8 more
TL;DR: Maternal vitamin D insufficiency is common during pregnancy and is associated with reduced bone-mineral accrual in the offspring during childhood; this association is mediated partly through the concentration of umbilical venous calcium.
Journal ArticleDOI
Prenatal environmental exposures, epigenetics, and disease.
TL;DR: The findings discussed indicate that identification of environmental chemicals that dysregulate the prenatal epigenome should be a priority in health research and disease prevention.
Journal ArticleDOI
Fetal Origins of Adult Disease
TL;DR: By understanding FOAD, health care professionals and policy makers will make this issue a high health care priority and implement preventive measures and treatment for those at higher risk for chronic diseases.
References
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Journal ArticleDOI
Prediction of Bone-Density from Vitamin-D Receptor Alleles
Nigel Alexander Morrison,Jian Cheng Qi,Akifumi Tokita,Paul J. Kelly,Linda Crofts,Tuan V. Nguyen,Philip N. Sambrook,John A. Eisman +7 more
TL;DR: It is shown that common allelic variants in the gene encoding the vitamin D receptor can be used to predict differences in bone density, accounting for up to 75% of the total genetic effect on bone density in healthy individuals.
Journal ArticleDOI
Genetic determinants of bone mass in adults. A twin study.
Nicholas Pocock,John A. Eisman,John L. Hopper,Michael G. Yeates,Philip N. Sambrook,Stefan Eberl +5 more
TL;DR: The lesser genetic contribution to proximal femur and distal forearm bone mass compared with the spine suggests that environmental factors are of greater importance in the aetiology of osteopenia of the hip and wrist.
Journal ArticleDOI
Fetal origins of adult disease—the hypothesis revisited
TL;DR: The hypothesis that adult disease has fetal origins is plausible, but much supportive evidence is flawed by incomplete and incorrect statistical interpretation.
Journal Article
Education and debate - Fetal origins of adult disease - the hypothesis revisited
Alan Lucas,Fewtrell,Tim J Cole +2 more
Journal ArticleDOI
Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates.
Charles W. Slemenda,Joe C. Christian,Christopher J. Williams,James A. Norton,C. Conrad Johnston +4 more
TL;DR: The familial resemblance in bone mass is due primarily to genetic effects at all skeletal sites and at all ages, although the importance of genetic effects is diminished with aging, as evidenced by increasing within‐MZ pair variability in older women.