Impact of genetic variation on metabolic response of bone to diet.
There is compelling evidence to suggest that both the development of bone to peak bone mass at maturity and subsequent loss depend on the interaction between genetic, hormonal, environmental and nutritional factors. The major part (< or = 80%) of the age-specific variation in bone turnover and bone density is genetically determined. However, the notion of genetic determinant is of little value unless the specific genes that are involved can be identified. Most work in this area of osteoporosis research has focused on the candidate gene approach, which has identified several candidate genes for osteoporosis, including genes encoding the vitamin D receptor (VDR), oestrogen receptors (alpha and beta), apolipoprotein E, collagen type I alpha 1 and methylenetetrahydrofolate reductase, amongst many others. However, in general, findings from numerous studies of the association between such genes and various bone variables have been inconsistent. In addition to possible gene-gene interactions it is likely that there are interactions between these genes and certain environmental factors, especially nutrition, that may mediate expression of bone-related phenotypes. While these potential interactions add a level of complexity to our understanding of these apparent genetic effects on bone, identification of a role for genetic factors without knowledge of their interaction with nutrients can do little to advance prevention and treatment of osteoporosis. This information is especially important because, unlike genotype, diet and nutrition can be modified. The aim of the present review is to critically evaluate current knowledge relating to candidate genes for osteoporosis, with particular emphasis on their interaction with nutrients and dietary factors in determining bone health.
Cusack
Siobhán
S
Department of Food and Nutritional Sciences, University College, Cork, Republic of Ireland.
Cashman
Kevin D
KD
D015519:Bone Density / Q000235:genetics*; D001846:Bone Development / Q000235:genetics; D001842:Bone and Bones / Q000378:metabolism*; D000090602:Collagen Type I, alpha 1 Chain; D004032:Diet; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D009747:Nutritional Physiological Phenomena; D010024:Osteoporosis / Q000235:genetics* / Q000517:prevention & control; D010641:Phenotype; D018167:Receptors, Calcitriol / Q000235:genetics
C000716127:COL1A1 protein, human; D000090602:Collagen Type I, alpha 1 Chain; D018167:Receptors, Calcitriol