Association of P2Y2 receptor SNPs with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients

Anke Wesselius,Peter Schwarz,Niklas R Jørgensen,Susanne Syberg,Pieter C Dagnelie,Svenhjalmar Van Helden,Zanne Henriksen,Solveig Petersen,Martijn J L Bours

doi:10.1007/s11302-012-9326-3

Abstract

The P2Y2 receptor is a G-protein-coupled receptor with adenosine 5′-triphosphate (and UTP) as natural ligands. It is thought to be involved in bone physiology in an anti-osteogenic manner. As several non-synonymous single nucleotide polymorphisms (SNPs) have been identified within the P2Y2 receptor gene in humans, we examined associations between genetic variations in the P2Y2 receptor gene and bone mineral density (BMD) (i.e., osteoporosis risk), in a cohort of fracture patients. Six hundred and ninety women and 231 men aged ≥50 years, visiting an osteoporosis outpatient clinic at Maastricht University Medical Centre for standard medical follow-up after a recent fracture, were genotyped for three non-synonymous P2Y2 receptor gene SNPs. BMD was measured at three locations (total hip, lumbar spine, and femoral neck) using dual-energy X-ray absorptiometry. Differences in BMD between different genotypes were tested using analysis of covariance. In women, BMD values at all sites were significantly different between the genotypes for the Leu46Pro polymorphism, with women homozygous for the variant allele showing the highest BMD values (0.05 > p > 0.01). The Arg312Ser and Arg334Cys polymorphisms showed no differences in BMD values between the different genotypes. This is the first report that describes the association between the Leu46Pro polymorphism of the human P2Y2 receptor and the risk of osteoporosis.

Highlights

Osteoporosis is a condition of the skeleton characterized by decreased bone density and bone structure changes, reducing its strength and resulting in increased risk of fragility fractures
Within a cohort of Dutch fracture patients, we have shown that the Leu46Pro polymorphism in the P2Y2 receptor gene was associated with increased bone mineral density (BMD) values in women, i.e., decreased risk of osteoporosis
This result is consistent with our main hypothesis that genetic aberration of P2Y2 receptor function affects BMD in humans

Summary

Introduction

Osteoporosis is a condition of the skeleton characterized by decreased bone density and bone structure changes, reducing its strength and resulting in increased risk of fragility fractures. This bone disease is one of the most common health problems among elderly in the Western society. Due to the growing elderly population as well as the sedentary lifestyle and changes in nutritional habits, the incidence of osteoporosis and related fractures is expected to increase exponentially worldwide over the decades. The annual cost of osteoporotic fractures nowadays is suggested to be approximately 36 billion euros [2] and is anticipated to increase to 106 billion euros in 2050 (www.iofbonehealth.org)

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