TY - JOUR
T1 - Relationship of estrogen receptor genotypes to bone mineral density and to rates of bone loss in men
AU - Khosla, Sundeep
AU - Riggs, B. Lawrence
AU - Atkinson, Elizabeth J.
AU - Oberg, Ann L.
AU - Mavilia, Carmelo
AU - Del Monte, Francesca
AU - Melton, L. Joseph
AU - Brandi, Maria Luisa
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2004/4
Y1 - 2004/4
N2 - Estrogen is now known to play an important role in bone metabolism in men. Thus, we examined possible relationships between polymorphisms of the estrogen receptor (ER)-α and -β genes, bone mineral density (BMD), and rates of bone loss in an age-stratified random sample of 283 Rochester, Minnesota, men aged 22-90 yr. DNA was analyzed for the XbaI and PvuII ER-α and AluI EB-β polymorphisms. The X/P and x/p alleles of the ER-α gene were in strong linkage disequilibrium. BMD at multiple sites did not differ as a function of either the ER-α or -β genotype. However, the ER-α (but not ER-β) genotypes did modulate the previously described relationships between BMD or rates of bone loss and bioavailable estradiol (E 2) levels in these men. At the femoral neck, BMD was associated with bioavailable E 3 levels in men with the XX (R = 0.66) or PP (R = 0.51) genotypes (P < 0.001 for both) but not in men with the xx (R = 0.15; P = 0.188) or pp (R = 0.12; P = 0.356) genotypes. The interactions between bioavailable E 2 levels and the XbaI and PvuII genotypes were significant at the P < 0.001 and P < 0.009 levels, respectively. Moreover, rates of bone loss at the midradius in men aged 60 -90 yr were modestly correlated with serum bioavailable E 2 levels in subjects with the X (R = 0.47) or P (R = 0.42) alleles (P < 0.001 for both) but not in those with the xx (R = 0.15; P = 0.430) or pp (R = 0.21; P = 0.372) genotypes. The overall effect of genotype on midradius rate of bone loss was clearly significant for the XbaI polymorphism (P = 0.009) when bioavailable E 2 levels were low (<40 pmol/liter) but not for the PvuII polymorphism. These data thus indicate that the ER-α genotype may modulate the relationship between BMD or rates of bone loss and estrogen levels in men and that bone mass in men with the X or P alleles may be more susceptible to the consequences of estrogen deficiency (and conversely, benefit most from estrogen sufficiency) than in men with the xx or pp genotypes.
AB - Estrogen is now known to play an important role in bone metabolism in men. Thus, we examined possible relationships between polymorphisms of the estrogen receptor (ER)-α and -β genes, bone mineral density (BMD), and rates of bone loss in an age-stratified random sample of 283 Rochester, Minnesota, men aged 22-90 yr. DNA was analyzed for the XbaI and PvuII ER-α and AluI EB-β polymorphisms. The X/P and x/p alleles of the ER-α gene were in strong linkage disequilibrium. BMD at multiple sites did not differ as a function of either the ER-α or -β genotype. However, the ER-α (but not ER-β) genotypes did modulate the previously described relationships between BMD or rates of bone loss and bioavailable estradiol (E 2) levels in these men. At the femoral neck, BMD was associated with bioavailable E 3 levels in men with the XX (R = 0.66) or PP (R = 0.51) genotypes (P < 0.001 for both) but not in men with the xx (R = 0.15; P = 0.188) or pp (R = 0.12; P = 0.356) genotypes. The interactions between bioavailable E 2 levels and the XbaI and PvuII genotypes were significant at the P < 0.001 and P < 0.009 levels, respectively. Moreover, rates of bone loss at the midradius in men aged 60 -90 yr were modestly correlated with serum bioavailable E 2 levels in subjects with the X (R = 0.47) or P (R = 0.42) alleles (P < 0.001 for both) but not in those with the xx (R = 0.15; P = 0.430) or pp (R = 0.21; P = 0.372) genotypes. The overall effect of genotype on midradius rate of bone loss was clearly significant for the XbaI polymorphism (P = 0.009) when bioavailable E 2 levels were low (<40 pmol/liter) but not for the PvuII polymorphism. These data thus indicate that the ER-α genotype may modulate the relationship between BMD or rates of bone loss and estrogen levels in men and that bone mass in men with the X or P alleles may be more susceptible to the consequences of estrogen deficiency (and conversely, benefit most from estrogen sufficiency) than in men with the xx or pp genotypes.
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U2 - 10.1210/jc.2003-031448
DO - 10.1210/jc.2003-031448
M3 - Article
C2 - 15070949
AN - SCOPUS:1942440501
SN - 0021-972X
VL - 89
SP - 1808
EP - 1816
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -