XML Feed for RxPG News   Add RxPG News Headlines to My Yahoo!   Javascript Syndication for RxPG News

Research Health World General
 
  Home
 
 Latest Research
 Cancer
 Psychiatry
 Genetics
 Surgery
 Aging
 Ophthalmology
 Gynaecology
 Neurosciences
 Pharmacology
 Cardiology
 Obstetrics
 Infectious Diseases
 Respiratory Medicine
 Pathology
 Endocrinology
 Immunology
 Nephrology
 Gastroenterology
 Biotechnology
 Radiology
 Dermatology
 Microbiology
 Haematology
 Dental
 ENT
 Environment
 Embryology
 Orthopedics
  Osteoporosis
  Osteomyelitis
 Metabolism
 Anaethesia
 Paediatrics
 Public Health
 Urology
 Musculoskeletal
 Clinical Trials
 Physiology
 Biochemistry
 Cytology
 Traumatology
 Rheumatology
 
 Medical News
 Health
 Opinion
 Healthcare
 Professionals
 Launch
 Awards & Prizes
 
 Careers
 Medical
 Nursing
 Dental
 
 Special Topics
 Euthanasia
 Ethics
 Evolution
 Odd Medical News
 Feature
 
 World News
 Tsunami
 Epidemics
 Climate
 Business
Search

Last Updated: Aug 19th, 2006 - 22:18:38

GENOMOS Study

Osteoporosis Channel
subscribe to Osteoporosis newsletter

Latest Research : Orthopedics : Osteoporosis

   DISCUSS   |   EMAIL   |   PRINT
GENOMOS: Weak Links found between COL1A1 Polymorphism, BMD, and Fracture Risk
Feb 24, 2006, 08:47, Reviewed by: Dr. Priya Saxena

Several previous studies had examined a possible association between the T allele and low bone mineral density and fractures, and a number of them had found such a link, as had three separate meta-analyses.

 
One out of every two women and one in eight men over 50 will have an osteoporosis-related fracture in their lifetime. Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue, and often progresses without overt symptoms or pain until a bone breaks. Fractures occur typically in the hip, spine, and wrist. Currently, there is no accurate measure of overall bone strength. Bone mineral density (BMD) is frequently used as a proxy measure, but it can explain only a modest proportion of fracture risk.

Bone resorption and bone formation take place throughout life. Formation outpaces resorption until peak bone mass (maximum bone density and strength) is reached around age 30. From then on, bone resorption slowly begins to exceed bone formation, and the balance is further shifted toward resorption in women after menopause. Osteoporosis develops when bone resorption occurs too quickly or replacement too slowly—which happens in most individuals at a certain age and often earlier in individuals who did not reach optimal bone mass during their bone building years.

Both bone formation and resorption are under the control of genetic and environmental factors. Osteoporosis is a “complex disease,” with variations in a number of different genes and in several environmental factors (such as calcium intake or alcohol consumption) thought to affect an individual's risk. A number of candidate genes have been identified, some of them through studies of rare genetic diseases affecting bone health, others through animal studies. They include genes for calciotropic hormones and their receptors, as well as bone matrix proteins.

One of them, COL1A1, encodes collagen 1 alpha 1, a major component of bone and cartilage. Mutations in its coding region cause osteogenesis imperfecta, a rare developmental bone disorder characterized by brittle bones, frequent fractures, and short stature. Apart from these rare mutations, COL1A1 has a number of polymorphic sites outside the coding region, and scientists have examined associations between many of these alleles and osteoporosis. The one that has been studied most intensely is a single-nucleotide polymorphism within the promoter region at a binding site for the Sp1 transcription factor. The more common allele has a guanine nucleotide (G) at the variable position; the rarer one, a thymine (T). In vitro studies suggest that the T allele is associated with less transcript and protein produced.

Several previous studies had examined a possible association between the T allele and low bone mineral density and fractures, and a number of them had found such a link, as had three separate meta-analyses. As a consequence, some researchers have suggested that genetic testing at the population level for this polymorphism would be beneficial. Individuals who carry the T allele could be advised to get enough calcium and do weight-bearing exercises, ideally already during the bone acquisition phase in adolescence. Others have warned that the evidence that links the T allele to a higher risk for osteoporosis is not strong enough to support such action. They have pointed out some of the notorious problems with association studies in general and retrospective meta-analyses based on published studies.

The Genetic Markers for Osteoporosis (GENOMOS) project is a European Union–funded European collaborative research initiative between universities in the Netherlands, United Kingdom, Italy, Spain, Greece, Poland, and Denmark. The project, which began in 2003, currently involves around 24,000 individuals and seeks to identify genetic risk factors for osteoporosis by prospective meta-analysis. Participants have been recruited from a total of 18 European countries (most of them reside in the UK, the Netherlands, Spain, Italy, Denmark, and Poland). Data on previous and new fractures are collected, together with bone densitometry measurements, information on risk factors, and DNA analysis from blood samples.

The GENOMOS investigators, led by John Ioannidis, report now on their examination of an association between the Sp1 polymorphism in COL1A1, BMD, and fracture risk. Based on data from over 20,000 participants, they found a modest association between homozygosity for the T allele and lower bone mineral density at the femoral neck and the lumbar spine. The researchers also found a weak association between the T allele and vertebral fractures in women. However, T allele carriers did not have an overall increased risk of fractures.

Vertebral compression fractures in a patient with osteoporosis; From: (2006) GENOMOS Study Finds Weak Links between COL1A1 Polymorphism, BMD, and Fracture Risk. PLoS Med 3(4): e152

The effects seen in this large study—GENOMOS participants reported more than five times the number of fractures than participants in all previous studies combined—were more moderate than those reported in most of the earlier studies. The Sp1 polymorphism in COL1A1 explained only a small part of the differences in BMD and fracture risk among the GENOMOS participants. There was no association between the T allele and BMD in heterozygous carriers (and only approximately 4% of the participants were homozygous for the T allele). Regarding the fracture association, the researchers estimate that the presence of the T allele would explain at most 10% of the risk of vertebral fractures for women.

The authors conclude that “large-scale studies are needed to quantify the true effect size of genetic polymorphisms that have been implicated in the pathogenesis of complex genetic disorders.” Their findings also argue against widespread genetic testing for this particular polymorphism alone. Researchers need to look at other genes (and possibly other variants in the COL1A1 gene) and validate any findings in large studies like this one before they can predict a substantial fraction of a random individual's genetic risk for osteoporosis.
 

- (2006) GENOMOS Study Finds Weak Links between COL1A1 Polymorphism, BMD, and Fracture Risk. PLoS Med 3(4): e152
 

Read Research Article at PLoS Medicine

 
Subscribe to Osteoporosis Newsletter
E-mail Address:

 

GENOMOS Study Finds Weak Links between COL1A1 Polymorphism, BMD, and Fracture Risk

DOI: 10.1371/journal.pmed.0030152

Published: February 21, 2006

Copyright: © 2006 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License.

PLoS Medicine is an open-access journal published by the nonprofit organization Public Library of Science.


Related Osteoporosis News

Modifying NFATc1 Triggers Bone Production
'Magic formula' accurately predicts fracture risk in osteoporotic women
Calcium supplements fail to prevent bone fractures in children
Estrens might not be the answer for osteoporosis
Increasing NFATc1 activity causes massive bone accumulation
Second-Hand Smoke, First-Hand Problem
Low carbohydrate diet did not increase bone loss
Growing body of research links lead to osteoporosis
GENOMOS: Weak Links found between COL1A1 Polymorphism, BMD, and Fracture Risk
Denosumab may show promise in the treatment of osteoporosis


For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 

© Copyright 2004 onwards by RxPG Medical Solutions Private Limited
Contact Us