Rs4988321

rs4988321 is a SNP in the LRP5 gene that is also known as Val667Met or V667M; the more common (G) allele encodes the Val (valine), while the rarer (A) allele encodes the Met (methionine), which is the risk allele.

rs4988321(A) is associated with vertebral fractures and reduced bone mineral density (BMD), with an overall odds ratio for vertebral fractures of 1.26 per allele (CI: 1.08-1.47; 2001 fractures among 20,488 individuals studied). More specifically, the rs4988321(A) allele was associated with reduced lumbar spine BMD density (p = 3.3 x 10-8), and femoral neck BMD (p = 3.8 x 10-5).

Note that rs3736228, another LRP5 SNP (also known as Ala1330Val), was independently associated with BMD in this same study.

No association was found between rs4988321 and either hip or spine BMD in a study of 249 Caucasian osteoporotic or osteopenic men.

triallelic and on a chip

Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men.

Genome-wide association with bone mass and geometry in the Framingham Heart Study.

Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with peak bone mass in non-sedentary men: results from the Odense androgen study.

Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis.

Replication study of candidate genes/loci associated with osteoporosis based on genome-wide screening.

The conjugation of benzoic acid in the African bat, Epomops franqueti.

Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.

LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women.

Oropharyngeal skeletal disease accompanying high bone mass and novel LRP5 mutation.

LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders.

LRP5 coding polymorphisms influence the variation of peak bone mass in a normal population of French-Canadian women.