Steroid hormone receptor gene polymorphisms and osteoporosis: a pharmacogenomic review.
Osteoporosis is a common skeletal disorder with a strong genetic component. In recent years, significant progress has been made in understanding the genetic basis of osteoporosis. Given the biological significance of signalling through steroid hormone receptors, bone biology and calcium homeostasis, alleles of steroid hormone receptor genes have been postulated to contribute to the well-documented genetic predisposition to osteoporosis; and in different studies, these alleles have been associated with variation in bone mass and fracture risk. Even though results are still conflicting and the molecular mechanisms by which these polymorphisms influence receptor activity remain, in part, to be investigated, an additional important issue is represented by potential pharmacogenomic (the investigation of variations of DNA or RNA characteristics as related to drug response) or pharmacogenetic (the influence of variations of DNA sequence on drug response) implications. In fact, steroid hormone receptors actually mediate the action of several compounds known to positively or negatively affect bone homeostasis, such as vitamin D, estrogen and glucocorticoids. This review analyses major pharmacogenetic studies of polymorphisms in steroid hormone receptor genes.
Gennari
Luigi
L
Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Viale Bracci 1, 53100 Siena, Italy. gennari@unisi.it
De Paola
Vincenzo
V
Merlotti
Daniela
D
Martini
Giuseppe
G
Nuti
Ranuccio
R
D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D002117:Calcitriol / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000502:physiology; D011960:Receptors, Estrogen / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics*
D050071:Bone Density Conservation Agents; D004967:Estrogens; D018167:Receptors, Calcitriol; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D002117:Calcitriol