Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Osteoporosis, postmenopausal form [M81.0]

OMIM numbers: 166710, 120150 (COL1A1)

Dr. rer. nat. Christoph Marschall, Dipl.-Biol. Christine Schack,
Dipl.-Biol. Christina Sofeso

Scientific Background

Osteoporosis is characterized by reduction of bone density due to demineralization of the bone. Within the EU, approximately every 8th citizen above the age of 50 suffers a fracture of the vertebral body; every 3rd woman above 80 suffers a femoral neck fracture due to osteoporosis. Family and twin studies showed that up to 80% of the individual bone density is determined genetically, with several genetic factors probably having an impact. In addition, other non-genetic factors such as living and eating habits or hormonal changes influence the bone density significantly as well.

Type I collagen is the main protein component of bones and is encoded by the COL1 gene family. A variant in the regulatory region of COL1A1 seems to have an impact on the bone density and the risk of fracture in postmenopausal women. The COL1A1-S/s polymorphism (frequency of the s allele approx. 20%) leads to increased gene expression which causes an increased synthesis of the α1 chain resulting in an abnormal α1 and α2 collagen chain ratio. The consequence is a decrease in bone density and an increased risk of osteoporotic fractures. Every s allele reduces the bone density and leads to a significant increase in the fracture risk (gene dosage effect). The s allele frequency in patients suffering from osteoporosis and fractures of the vertebral body is nearly twice as high as in the control groups.