Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteoporosis is a common disease with a strong genetic component. Twin studies have shown that genetic factors play an important role in regulating bone mineral density (BMD), ultrasound properties of bone, skeletal geometry, and bone turnover as well as contributing to the pathogenesis of osteoporotic fracture itself. These phenotypes are determined by the combined effects of several genes and environmental influences, but occasionally, osteoporosis or unusually high bone mass can occur as the result of mutations in a single gene. Examples are the osteoporosis-pseudoglioma syndrome, caused by inactivating mutations in the lipoprotein receptor-related protein 5 gene and the high bone mass syndrome, caused by activating mutations of the same gene. Genome-wide linkage studies in man have identified loci on chromosomes 1p36, 1q21, 2p21, 5q33-35, 6p11-12, and 11q12-13 that show definite or probable linkage to BMD, but so far, the causative genes remain to be identified. Linkage studies in mice have similarly identified several loci that regulate BMD, and a future challenge will be to investigate the syntenic loci in humans. A great deal of research has been done on candidate genes; among the best studied are the vitamin D receptor and the collagen type I alpha 1 gene. Polymorphisms of vitamin D receptor have been associated with bone mass in several studies, and there is evidence to suggest that this association may be modified by dietary calcium and vitamin D intake. A functional polymorphism affecting an Sp1 binding site has been identified in the collagen type I alpha 1 gene that predicts osteoporotic fractures independently of bone mass by influencing collagen gene regulation and bone quality. An important problem with most candidate gene studies is small sample size, and this has led to conflicting results in different populations. Some researchers are exploring the use of meta-analysis to try and address this issue and gain an accurate estimate of effect size for different polymorphisms in relation to relevant clinical endpoints, such as BMD and fracture. From a clinical standpoint, advances in knowledge about the genetic basis of osteoporosis are important, because they offer the prospect of developing genetic markers for the assessment of fracture risk and the opportunity to identify molecules that will be used as targets for the design of new drugs for the prevention and treatment of bone disease.
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PMID:Genetic control of susceptibility to osteoporosis. 1205 Feb

Osteoporosis is the most common metabolic bone disease and caused by multiple nutritional, environmental and genetical factors. Bone mineral density (BMD) is rather strongly under genetical control. A number of candidate genes have been studied with respect to the impact on BMD. Also, gene loci of susceptibility genes for osteoporosis have been identified by family-based association and linkage approaches. In particular, LRP5 is an important molecule involved in the determination of BMD, because its abnormality is associated with osteoporosis-pseudoglioma syndrome or autosomal dominant syndrome characterized by high bone density. These findings may contribute to new strategy to teat patients with osteoporosis.
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PMID:[Osteoporosis associated with gene mutation]. 1577 38