TY - JOUR
T1 - Influence of Polymorphisms in the RANKL/RANK/OPG Signaling Pathway on Volumetric Bone Mineral Density and Bone Geometry at the Forearm in Men
AU - Roshandel, Delnaz
AU - Holliday, Kate L.
AU - Pye, Stephen R.
AU - Ward, Kate A.
AU - Boonen, Steven
AU - Vanderschueren, Dirk
AU - Borghs, Herman
AU - Huhtaniemi, Ilpo T.
AU - Adams, Judith E.
AU - Bartfai, Gyorgy
AU - Casanueva, Felipe F.
AU - Finn, Joseph D.
AU - Forti, Gianni
AU - Giwercman, Aleksander
AU - Han, Thang S.
AU - Kula, Krzysztof
AU - Lean, Michael E.
AU - Pendleton, Neil
AU - Punab, Margus
AU - Silman, Alan J.
AU - Wu, Frederick C.
AU - Thomson, Wendy
AU - O'Neill, Terence W.
AU - EMAS Study Group
PY - 2011/12
Y1 - 2011/12
N2 - We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r 2 ≥ 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm 3) and cross-sectional area (mm 2) at the 4% site and cortical vBMD (mg/mm 3); total, cortical, and medullary area (mm 2); cortical thickness (mm); and stress strain index (SSI) (mm 3) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (β [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (β [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (β [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (β [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (β [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (β [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (β [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (β [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men. © 2011 The Author(s).
AB - We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r 2 ≥ 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm 3) and cross-sectional area (mm 2) at the 4% site and cortical vBMD (mg/mm 3); total, cortical, and medullary area (mm 2); cortical thickness (mm); and stress strain index (SSI) (mm 3) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (β [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (β [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (β [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (β [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (β [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (β [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (β [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (β [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men. © 2011 The Author(s).
KW - Genetic association
KW - Genetic polymorphism
KW - Male
KW - Osteoporosis
KW - QCT
U2 - 10.1007/s00223-011-9532-y
DO - 10.1007/s00223-011-9532-y
M3 - Article
C2 - 21964949
SN - 1432-0827
VL - 89
SP - 446
EP - 455
JO - Calcified tissue international
JF - Calcified tissue international
IS - 6
ER -