Purpose: To investigate the impact of the Ala1330Val (rs3736228, exon 18) and Val667Met (rs4988321, exon 9) polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene on peak bone mass in young men.
Methods: The Odense Androgen Study (OAS) is a population-based study comprising 783 Caucasian men aged 20-30 years. Genotyping was performed using real-time polymerase chain reaction (PCR) or fluorescence polarization. Bone mineral density (BMD) measurements were performed using dual-energy X-ray absorptiometry.
Results: The CC, CT, and TT genotypes in Ala1330Val were found in 75.6%, 21.8%, and 2.6% of the participants, respectively. Similarly, the GG, GA, and AA genotypes of Val667Met were found in 89.7%, 9.8%, and 0.5%, respectively. For the Ala1330Val polymorphism, no significant differences between the genotypes were found regarding BMD in the overall study population. However, when analysis was restricted to non-sedentary men (n = 589), a significant association between the number of T-alleles and BMD in the spine and whole body were found. Each copy of the T-allele changed the Z-score of the spine by (median and 95% confidence interval) -0.21 [95% CI: -0.40; -0.03] (p < 0.02). Analysis suggested an association between the AA genotype in the Val667Met polymorphism and increased body height and decreased BMD of the femoral neck; however, no significant gene-dose effect of the A-allele could be demonstrated in the whole population. When the analysis was restricted to non-sedentary subjects, however, each number of A-alleles was associated with a change in Z-score of -0.26 [95% CI: -0.51; -0.01] (p = 0.04). No further significant results emerged with haplotype analysis.
Conclusion: The Ala1330Val and Val667Met polymorphisms in the LRP5 gene are significantly associated with peak bone mass in physically active men.
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http://dx.doi.org/10.1007/s00223-007-9088-z | DOI Listing |
J Biochem Mol Toxicol
January 2025
Department of Medical Biochemistry, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
Ovarian ischemia is a pathological condition that usually occurs due to ovarian torsion, resulting in the interruption of blood supply to the ovaries and oxygen deficiency. Silymarin (SLM) is a flavonoid complex of plant origin with pharmacological properties such as antioxidant, anti-inflammatory, and antiapoptotic effects. In this study, we investigated the effects of SLM through different pathways in rats subjected to experimental ovarian ischemia/reperfusion (I/R).
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
December 2024
Section of Endocrinology & Investigative Medicine, Imperial College London, London, United Kingdom.
Normal pregnancy and lactation have a marked physiological impact on maternal bone metabolism. This impact is usually temporary and reversible, but some women sustain fragility fractures whilst pregnant or lactating, termed pregnancy and lactation-associated osteoporosis (PLO). These fractures have severe negative consequences on their quality of life, at what is a crucial stage in a mother's life.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Paris Cardiovascular Research Center, Université Paris Cité, Inserm U970, Paris F-75015, France.
The integrity of the blood-retina barrier (BRB) is crucial for phototransduction and vision, by tightly restricting transport of molecules between the blood and surrounding neuronal cells. Breakdown of the BRB leads to the development of retinal diseases. Here, we show that Netrin-1/Unc5b and Norrin/Lrp5 signaling establish a zonated endothelial cell gene expression program that controls BRB integrity.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Developmental Biology and Cancer Department, University College London Great Ormond Street Institute of Child Health, University College London, and National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, London WC1N 1EH, United Kingdom.
Variants in the gene cause Norrie disease, a severe dual-sensory disorder characterized by congenital blindness due to disrupted retinal vascular development and progressive hearing loss accompanied by sensory hair cell death. encodes the secreted signaling molecule norrin. The role of norrin in the cochlea is incompletely understood.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
November 2024
Division of Endocrinology, The Council of Scientific and Industrial Research (CSIR)-Central Drug Research Institute, Lucknow, India.
Background: Genetic mutations have been reported in a number of bone disorders with or without extra-skeletal manifestations. The purpose of the present study was to investigate the genetic cause in a middle-aged woman with osteoporosis, recurrent fractures and extraskeletal manifestations.
Methods: A 56-year-old Indian woman presented to the clinic with complaints of difficulty in walking, recurrent fractures, limb bending, progressive skeletal deformities, and poor overall health.
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