Non-synonymous polymorphisms in the P2RX ( 4 ) are related to bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients

TY - JOUR

T1 - Non-synonymous polymorphisms in the P2RX ( 4 ) are related to bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients

AU - Wesselius, Anke

AU - Bours, Martijn Jl

AU - Jørgensen, Niklas R

AU - Wiley, James

AU - Gu, Ben

AU - van Helden, Svenjhalmar

AU - van Rhijn, Lodewijk

AU - Dagnelie, Pieter C

PY - 2013/3

Y1 - 2013/3

N2 - In the present study we investigated whether single nucleotide polymorphisms (SNPs) in the P2RX4, which alter the P2X4R function, are associated with the development of osteoporosis and whether an interaction between the P2X4R and P2X7R confer a synergistic effect of these two receptors on osteoporosis risk. Patients with fracture (690 females and 231 males, aged ≥50 years) were genotyped for three non-synonymous P2X4R SNPs. Bone mineral density (BMD) was measured at the total hip, lumbar spine, and femoral neck. Subject carrying the variant allele of the Tyr315Cys polymorphism showed a 2. 68-fold (95 % CI, 1. 20-6. 02) higher risk of osteoporosis compared with wild-type subject. Furthermore, significant lower lumbar spine BMD values were observed in subjects carrying the Cys315 allele as compared with wild-type (0. 85 ± 0. 17 and 0. 93 ± 0. 17 g/cm2, respectively; p & 0. 001). Assuming a recessive model, carriers of the variant allele of the Ser242Gly polymorphism showed increased BMD values at the lumbar spine compare to wild-type subject (1. 11 ± 0. 35 and 0. 92 ± 0. 17 g/cm2, respectively; p = 0. 0045). This is the first study demonstrating an association of non-synonymous polymorphisms in the P2RX4 and the risk of osteoporosis, suggesting a role of the P2X4R in the regulation of bone mass.

AB - In the present study we investigated whether single nucleotide polymorphisms (SNPs) in the P2RX4, which alter the P2X4R function, are associated with the development of osteoporosis and whether an interaction between the P2X4R and P2X7R confer a synergistic effect of these two receptors on osteoporosis risk. Patients with fracture (690 females and 231 males, aged ≥50 years) were genotyped for three non-synonymous P2X4R SNPs. Bone mineral density (BMD) was measured at the total hip, lumbar spine, and femoral neck. Subject carrying the variant allele of the Tyr315Cys polymorphism showed a 2. 68-fold (95 % CI, 1. 20-6. 02) higher risk of osteoporosis compared with wild-type subject. Furthermore, significant lower lumbar spine BMD values were observed in subjects carrying the Cys315 allele as compared with wild-type (0. 85 ± 0. 17 and 0. 93 ± 0. 17 g/cm2, respectively; p & 0. 001). Assuming a recessive model, carriers of the variant allele of the Ser242Gly polymorphism showed increased BMD values at the lumbar spine compare to wild-type subject (1. 11 ± 0. 35 and 0. 92 ± 0. 17 g/cm2, respectively; p = 0. 0045). This is the first study demonstrating an association of non-synonymous polymorphisms in the P2RX4 and the risk of osteoporosis, suggesting a role of the P2X4R in the regulation of bone mass.

U2 - 10.1007/s11302-012-9337-0

DO - 10.1007/s11302-012-9337-0

M3 - Journal article

SN - 1573-9538

VL - 9

SP - 123

EP - 130

JO - Purinergic Signalling

JF - Purinergic Signalling

IS - 1

ER -