TY - JOUR
T1 - Association of P2X7 receptor polymorphisms with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients
AU - Wesselius, A
AU - Bours, M J L
AU - Henriksen, Z
AU - Syberg, S
AU - Petersen, S
AU - Schwarz, P
AU - Jørgensen, N R
AU - van Helden, S
AU - Dagnelie, P C
PY - 2013/4
Y1 - 2013/4
N2 - Summary: The P2X7 receptor is thought to be involved in bone physiology in a pro-osteogenic manner. Therefore, we examined associations between genetic variations in the P2X7 receptor gene and bone mineral density (BMD). We found an association between four non-synonymous polymorphism of the human P2X7 receptor and the risk of osteoporosis. Introduction: The purpose of this study was to determine whether genetic variation in the P2X7 receptor gene (P2RX7) is associated with decreased BMD and risk of osteoporosis in fracture patients. Methods: Six hundred ninety women and 231 men aged ≥50 years were genotyped for 15 non-synonymous P2RX7 SNPs. BMD was measured at the total hip, lumbar spine and femoral neck. Results: Four non-synonymous SNPs were associated with BMD. The Ala348Thr gain-of-function polymorphism was associated with increased BMD values at the lumbar spine (p = 0.012). Decreased hip BMD values were associated with two loss-of-function SNPs in the P2RX7, i.e., in subjects homozygous for the Glu496Ala polymorphism as well as in subjects carrying at least one variant allele of the Gly150Arg polymorphism (p = 0.018 and p = 0.011; respectively). In men, we showed that subjects either heterozygous or homozygous for the Gln460Arg gain-of-function polymorphism in the P2RX7 had a significantly 40 % decrease in risk of a lower T-score value (OR = 0.58 [95%CI, 0.33-1.00]). Conclusion: Thus, genetic aberrations of P2X7R function are associated with lower BMD and increased osteoporosis risk. Therefore, detection of non-synonymous SNPs within the P2RX7 might be useful for osteoporosis risk estimation at an early stage, potentially enabling better osteoporosis prevention and treatment.
AB - Summary: The P2X7 receptor is thought to be involved in bone physiology in a pro-osteogenic manner. Therefore, we examined associations between genetic variations in the P2X7 receptor gene and bone mineral density (BMD). We found an association between four non-synonymous polymorphism of the human P2X7 receptor and the risk of osteoporosis. Introduction: The purpose of this study was to determine whether genetic variation in the P2X7 receptor gene (P2RX7) is associated with decreased BMD and risk of osteoporosis in fracture patients. Methods: Six hundred ninety women and 231 men aged ≥50 years were genotyped for 15 non-synonymous P2RX7 SNPs. BMD was measured at the total hip, lumbar spine and femoral neck. Results: Four non-synonymous SNPs were associated with BMD. The Ala348Thr gain-of-function polymorphism was associated with increased BMD values at the lumbar spine (p = 0.012). Decreased hip BMD values were associated with two loss-of-function SNPs in the P2RX7, i.e., in subjects homozygous for the Glu496Ala polymorphism as well as in subjects carrying at least one variant allele of the Gly150Arg polymorphism (p = 0.018 and p = 0.011; respectively). In men, we showed that subjects either heterozygous or homozygous for the Gln460Arg gain-of-function polymorphism in the P2RX7 had a significantly 40 % decrease in risk of a lower T-score value (OR = 0.58 [95%CI, 0.33-1.00]). Conclusion: Thus, genetic aberrations of P2X7R function are associated with lower BMD and increased osteoporosis risk. Therefore, detection of non-synonymous SNPs within the P2RX7 might be useful for osteoporosis risk estimation at an early stage, potentially enabling better osteoporosis prevention and treatment.
U2 - 10.1007/s00198-012-2059-x
DO - 10.1007/s00198-012-2059-x
M3 - Journal article
C2 - 22776862
SN - 0937-941X
VL - 24
SP - 1235
EP - 1246
JO - Osteoporosis International
JF - Osteoporosis International
IS - 4
ER -