Functional characterization of genetic variation in the Frizzled 1 (FZD1) promoter and association with bone phenotypes: more to the LRP5 story?

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Laura M YergesJoseph M Zmuda

Abstract

WNT signaling is an important determinant of bone formation. The WNT co-receptor, Frizzled homolog 1 (FZD1), initiates WNT signal transduction. To study the influence of FZD1 genetic variation on measures of bone health, we first sequenced a 6.8-kb region surrounding FZD1 in 48 samples of African ancestry. We genotyped all common polymorphisms and performed association analysis with bone phenotypes in a larger sample. Only 3 of 35 SNPs identified were present in >or=5% of the sample and assayed further in 1084 men of African ancestry. Two of these SNPs were in the FZD1 promoter (rs2232157, rs2232158) and were associated with femoral neck areal BMD (p = 0.041 and 0.009, respectively). The minor alleles of these two SNPs were also associated with larger bone size at the radius (p < 0.05 for both), and rs2232158 was associated with greater strength-strain index, an indicator of bone's ability to withstand torsion. Functional experiments were completed to assess the influence of the rs2232158 promoter polymorphism on transcriptional regulation of FZD1. The minor C allele in rs2232158 creates a binding site for the transcription factor Egr1, has higher Egr1 binding affinity, and has greater FZD1 promoter activity in MG63 and SaOS-2 ...Continue Reading

References

Feb 1, 1992·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·D R CarterR Marcus
May 3, 2000·The Journal of Clinical Investigation·S CenciR Pacifici
Mar 10, 2001·Nature Genetics·L Kruglyak, D A Nickerson
Nov 24, 2001·Cell·Y GongUNKNOWN Osteoporosis-Pseudoglioma Syndrome Collaborative Group
Dec 14, 2001·Biochemical and Biophysical Research Communications·M RomanelloP D'Andrea
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Andrew I SuJohn B Hogenesch
Jan 22, 2004·International Journal of Cancer. Journal International Du Cancer·Bang H HoangRichard Gorlick
Feb 24, 2004·Frontiers in Bioscience : a Journal and Virtual Library·Craig C Malbon
Oct 12, 2004·Gene·Jennifer J WestendorfTania M Schroeder
Dec 28, 2004·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Daniel L KollerMichael J Econs
Jun 9, 2005·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Julie R HensJohn J Wysolmerski
Feb 10, 2006·Trends in Cell Biology·Christine Hartmann
May 4, 2006·The Journal of Clinical Investigation·Venkatesh KrishnanOrmond A Macdougald
Aug 26, 2006·Cancer Causes & Control : CCC·Clareann H BunkerJane A Cauley
Nov 23, 2006·Current Topics in Developmental Biology·Roland BaronSergio Roman-Roman
Sep 18, 2007·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·D D HillJ M Zmuda
Mar 20, 2008·JAMA : the Journal of the American Medical Association·Joyce B J van MeursUNKNOWN GENOMOS Study

❮ Previous
Next ❯

Citations

Apr 2, 2010·Endocrine Reviews·Xiang-Hong XuHong-Wen Deng
Mar 14, 2013·Archives of Toxicology·Eva ZellerAlbert Braeuning
Mar 30, 2010·Calcified Tissue International·M TenneK Akesson
Sep 30, 2014·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Gabriel L GaleaJoanna S Price
Feb 26, 2013·Seminars in Arthritis and Rheumatism·Eveline BoudinWim Van Hul
Oct 28, 2019·Bone Research·Jian LuoJianru Xiao
Jun 30, 2016·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Stefanie ThieleLorenz C Hofbauer
Jan 17, 2012·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Helen E GruberJames F Kellam

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.