Association between a variation in the phosphodiesterase 4D gene and bone mineral density.

Association between a variation in the phosphodiesterase 4D gene and bone mineral density. Research Abstract Details 

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Association between a variation in the phosphodiesterase 4D gene and bone mineral density. Abstract Text:

Richard H Reneland,Steven Mah,Stefan Kammerer,Carolyn R Hoyal,George Marnellos,Scott G Wilson,Philip N Sambrook,Tim D Spector,Matthew R Nelson,Andreas Braun,

BACKGROUND: Fragility fractures caused by osteoporosis are a major cause of morbidity and mortality in aging populations. Bone mineral density (BMD) is a useful surrogate marker for risk of fracture and is a highly heritable trait. The genetic variants underlying this genetic contribution are largely unknown. METHODS: We performed a large-scale association study investigating more than 25,000 single nucleotide polymorphisms (SNPs) located within 16,000 genes. Allele frequencies were estimated in contrasting DNA pools from white females selected for low (<0.87 g/cm2, n = 319) and high (> 1.11 g/cm2, n = 321) BMD at the lumbar spine. Significant findings were verified in two additional sample collections. RESULTS: Based on allele frequency differences between DNA pools and subsequent individual genotyping, one of the candidate loci indicated was the phosphodiesterase 4D (PDE4D) gene region on chromosome 5q12. We subsequently tested the marker SNP, rs1498608, in a second sample of 138 white females with low (<0.91 g/cm2) and 138 females with high (>1.04 g/cm2) lumbar spine BMD. Odds ratios were 1.5 (P = 0.035) in the original sample and 2.1 (P = 0.018) in the replication sample. Association fine mapping with 80 SNPs located within 50 kilobases of the marker SNP identified a 20 kilobase region of association containing exon 6 of PDE4D. In a second, family-based replication sample with a preponderance of females with low BMD, rs1498608 showed an opposite relationship with BMD at different sites (p = 0.00044-0.09). We also replicated the previously reported association of the Ser37Ala polymorphism in BMP2, known to interact biologically with PDE4D, with BMD. CONCLUSION: This study indicates that variants in the gene encoding PDE4D account for some of the genetic contribution to bone mineral density variation in humans. The contrasting results from different samples indicate that the effect may be context-dependent. PDE4 inhibitors have been shown to increase bone mass in normal and osteopenic mice, but up until now there have been no reports implicating any member of the PDE4 gene family in human osteoporosis.

Association between a variation in the phosphodiesterase 4D gene and bone mineral density. Publishing Authors By Initials

RH Reneland,S Mah,S Kammerer,CR Hoyal,G Marnellos,SG Wilson,PN Sambrook,TD Spector,MR Nelson,A Braun,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research

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Association between a variation in the phosphodiesterase 4D gene and bone mineral density. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: BMC medical genetics

VOLUME: 6

Page Numbers: 9

Journal Abbreviation: BMC Med. Genet.

ISSN: 1471-2350

DAY: 7

MONTH: 03

YEAR: 2005

Association between a variation in the phosphodiesterase 4D gene and bone mineral density. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100968552

Association between a variation in the phosphodiesterase 4D gene and bone mineral density. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta

MESH TERMS: genetics

Chemical & Substance for Abstract: Association between a variation in the phosphodiesterase 4D gene and bone mineral density. Information

Substance Name: PDE4D protein, human

Registry Number: EC 3.1.4.17

Grant and Affiliation Information for Association between a variation in the phosphodiesterase 4D gene and bone mineral density.

AFFILIATION: Sequenom, Inc, San Diego, California, USA. abraun@sequenom.com

Country: England

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MEDLINETA: BMC Med Genet

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