Sequenom, Inc. has discovered a genetic variation in the gene encoding phosphodiesterase 4D (PDE4D) that is believed to affect osteoporosis risk. Fragility fractures caused by osteoporosis are a major cause of morbidity and mortality in the aging population. Published in the online edition of BMC Medical Genetics the study entitled, "Association between a variation in the phosphodiesterase 4D gene and bone mineral density" reports that individuals with variants in the PDE4D gene account for some of the genetic contribution to bone mineral density (BMD). BMD is a useful surrogate marker for risk of fracture and is a highly heritable trait.

This is the first study to demonstrate that genetic variations in the PDE4 gene family might be involved in human osteoporosis. Previously, PDE4 inhibitors have been shown to increase bone mass in normal and osteopenic mice. However, the genetic variants underlying this genetic condition in
humans were largely unknown.

Researchers at Sequenom conducted a genome-wide, large-scale association study with a set of 25,000 single nucleotide polymorphisms (SNPs) involving over 600 Caucasian female individuals. The initial association was subsequently confirmed in two large, independent replication studies to validate the initial findings (combined OR = 1.7). In addition, the previously reported BMD association of BMP2, a bone morphogenetic protein known to have synergistic effects with PDE4D, was also confirmed in this study, the company release said.

Andi Braun, chief medical officer of Sequenom said, "To date, we have published our findings on two breast cancer genes, and now one gene involved in bone density. We believe these and other yet to be announced important discoveries will generate commercial value for Sequenom in a broad range of molecular medicine applications. These applications include diagnostics, disease predisposition testing, personalized medicine, pharmacogenomics, cancer subtyping and non-invasive prenatal testing. In this specific case, the identification of variations in the PDE4D gene may lead to significantly improved methods for diagnosis, prognosis and treatment of osteoporosis."

Designed to quickly and accurately perform high throughput genetic analysis, Sequenom's proprietary MassARRAY system and its large collection of SNP reagents made the discovery of the PDE4D genetic variations possible. Sequenom has identified and validated more than 60 high confidence candidate gene regions in 11 major disease areas.