Genetic variation in candidate osteoporosis genes, bone mineral density, and fracture risk: the study of osteoporotic fractures.
Candidate osteoporosis gene variants were examined for associations with fracture risk and bone mineral density (BMD). A total of 9,704 white women were recruited at four U.S. clinical centers and enrolled into the Study of Osteoporotic Fractures, a longitudinal cohort study. Genotyping of 31 polymorphisms from 18 candidate osteoporosis genes was performed in 6,752 women. Incident radiographic fractures were identified at the third and eighth examinations compared with the baseline examination. BMD was measured at the total hip by dual-energy X-ray absorptiometry. Analyses were adjusted for age, clinic site, and self-reported ethnicity. During a mean follow-up of 14.5 years, a total of 849 hip, 658 vertebral, and 2,496 nonhip/nonvertebral fractures occurred in 6,752 women. Women carrying the ALOX15_G48924T T/T genotype had a higher rate of hip fracture (hazard ratio [HR] = 1.33;95% confidence interval [95% CI] = 1.00-1.77) compared with the G/G genotype. Compared with those carrying the PRL_T228C T/T genotype, women with either the C/C (HR = 0.80; 95% CI = 0.67-0.95) or C/T (HR = 0.81; 95% CI = 0.68-0.97) genotype had a lower rate of nonvertebral/nonhip fractures. Women carrying the BMP2_A125611G G/G genotype had a higher rate of vertebral fracture (odds ratio [OR] = 1.51; 95% CI = 1.03-2.23) compared with the A/A genotype. Women with the ESR1_C1335G G/G genotype had a higher rate of vertebral fracture (OR = 1.64; 95% CI = 1.07-2.50) compared with the C/C genotype. Compared with those with the MMP2_C595T C/C genotype, women with the C/T (OR = 0.79; 95% CI = 0.65-0.96) or T/T (OR = 0.44; 95% CI = 0.27-0.72) genotype had a lower rate of vertebral fracture. In conclusion, polymorphisms in several candidate genes were associated with hip, vertebral, and nonhip/nonvertebral fractures but not with total hip BMD in this large population based cohort study.
Tranah
Gregory J
GJ
CPMC Research Institute, San Francisco, CA 94120, USA. gtranah@psg.ucsf.edu
Taylor
Brent C
BC
Lui
Li-Yung
LY
Zmuda
Joseph M
JM
Cauley
Jane A
JA
Ensrud
Kristine E
KE
Hillier
Teresa A
TA
Hochberg
Marc C
MC
Li
Jia
J
Rhees
Brian K
BK
Erlich
Henry A
HA
Sternlicht
Mark D
MD
Peltz
Gary
G
Cummings
Steven R
SR
D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D050723:Fractures, Bone / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D010024:Osteoporosis / Q000235:genetics*; D011110:Polymorphism, Genetic
BMC Med Genet. 2007 Sep 19;8 Suppl 1:S14
17903296
J Bone Miner Res. 2001 Jul;16(7):1195-206
11450694
J Bone Miner Res. 1992 Jun;7(6):633-8
1414481
N Engl J Med. 1998 Apr 9;338(15):1016-21
9535665
Osteoporos Int. 2004 Aug;15(8):659-64
14727014
Osteoporos Int. 2001;12(2):91-6
11303720
PLoS Biol. 2003 Dec;1(3):E69
14691541
J Bone Miner Res. 2006 Apr;21(4):556-64
16598376
Bone. 2006 Jul;39(1):174-80
16503213
J Steroid Biochem Mol Biol. 2007 Apr;104(1-2):22-6
17350824
J Bone Miner Res. 1992 Jun;7(6):625-32
1414480
J Endocrinol. 2000 Aug;166(2):235-45
10927613
J Clin Endocrinol Metab. 2002 Nov;87(11):5151-9
12414886
Clin Chim Acta. 2006 Sep;371(1-2):137-42
16603142
Hum Mutat. 2006 Jan;27(1):78-87
16320347
J Bone Miner Res. 1995 Nov;10(11):1778-87
8592956
Eur J Endocrinol. 2001 Mar;144(3):257-61
11248745
Exp Clin Endocrinol Diabetes. 2003 Oct;111(7):447-9
14614653
Horm Metab Res. 2007 Aug;39(8):543-7
17712717
J Bone Miner Res. 2007 May;22(5):730-6
17280526
J Biol Chem. 2006 Nov 3;281(44):33814-24
16959767
J Bone Miner Res. 1999 Oct;14(10):1637-45
10491209
Genet Epidemiol. 2002 Jan;22(1):12-25
11754470
PLoS Med. 2005 Aug;2(8):e124
16060722
J Bone Miner Metab. 2005;23(3):226-30
15838625
Endocrinology. 1999 Jan;140(1):96-105
9886812
Hum Hered. 2008;65(1):1-8
17652958
Cancer Epidemiol Biomarkers Prev. 2004 Dec;13(12):1985-6
15598750
JAMA. 2008 Mar 19;299(11):1277-90
18349089
J Steroid Biochem Mol Biol. 2001 Jul;78(1):15-20
11530279
J Bone Miner Res. 2004 Oct;19(10):1619-27
15355556
Am J Physiol Endocrinol Metab. 2000 Dec;279(6):E1216-25
11093907
J Bone Miner Res. 2003 Apr;18(4):723-9
12674333
J Reprod Med. 1999 Dec;44(12 Suppl):1111-5
10649820
Am J Hum Genet. 2004 May;74(5):866-75
15077203
Calcif Tissue Int. 2007 Jul;81(1):10-7
17520163
J Clin Endocrinol Metab. 2006 Sep;91(9):3575-83
16804049
PLoS Med. 2006 Apr;3(4):e90
16475872
J Clin Endocrinol Metab. 2008 May;93(5):2002-8
18319311
J Reprod Med. 1999 Dec;44(12 Suppl):1075-84
10649814
Ann Intern Med. 2006 Aug 15;145(4):255-64
16908916
BMC Med Genet. 2005 Mar 07;6:9
15752431
J Bone Miner Res. 2001 Aug;16(8):1532-9
11499876
J Clin Endocrinol Metab. 2005 Jun;90(6):3491-7
15797957
J Bone Miner Res. 2006 Jun;21(6):845-54
16753015
Bone. 2008 May;42(5):969-81
18284942
Nat Genet. 1996 Oct;14(2):203-5
8841196
Am J Hum Genet. 1989 Mar;44(3):429-33
2916585
Bone. 2007 Mar;40(3):737-42
17174622
Endocr Rev. 1999 Dec;20(6):788-804
10605626
Lancet. 1993 Jan 9;341(8837):72-5
8093403
Am J Epidemiol. 1992 Mar 1;135(5):490-9
1570815
Cancer Epidemiol Biomarkers Prev. 2006 Jan;15(1):186
16434613
JAMA. 1990 Feb 2;263(5):665-8
2404146
Am J Public Health. 1984 Dec;74(12):1374-80
6507690
JAMA. 2004 Nov 3;292(17):2105-14
15523071
Arch Intern Med. 1996 Oct 14;156(18):2073-80
8862099
J Bone Miner Res. 1991 Feb;6(2):191-7
2028837
J Hum Genet. 2004;49(2):80-86
14727154
Calcif Tissue Int. 2000 Mar;66(3):190-4
10666493
Bone. 2002 Mar;30(3):486-91
11882462
Biochem Biophys Res Commun. 1996 Dec 4;229(1):323-8
8954126
J Korean Med Sci. 2004 Jun;19(3):407-12
15201508
J Bone Miner Res. 2005 Jan;20(1):131-40
15619679
Genome Res. 1999 Oct;9(10):936-49
10523522
J Bone Miner Res. 2001 Jan;16(1):128-34
11149476
Osteoporos Int. 2008 Dec;19(12):1769-75
18418639
N Engl J Med. 1995 Mar 23;332(12):767-73
7862179
J Clin Invest. 2001 Apr;107(7):899-907
11285309
J Musculoskelet Neuronal Interact. 2002 Mar;2(3):225-31
15758440
Lancet. 2008 May 3;371(9623):1505-12
18455228
Eur J Endocrinol. 2002 Oct;147(4):461-5
12370106
Genes Dev. 2006 Sep 15;20(18):2492-506
16980579
J Clin Invest. 1987 Sep;80(3):706-10
3624485
JAMA. 2007 Dec 19;298(23):2761-7
18165669
Calcif Tissue Int. 2002 Nov;71(5):386-92
12232679
J Bone Miner Res. 2004 Oct;19(10):1612-8
15355555
Clin Chem Lab Med. 2007;45(4):487-92
17439326
Eur J Hum Genet. 1998 Mar-Apr;6(2):151-7
9781060
Osteoporos Int. 2006;17(4):521-6
16365830
J Bone Miner Res. 2002 Mar;17(3):384-93
11874231
J Med Genet. 2005 Mar;42(3):240-6
15744038
J Bone Miner Res. 1995 Nov;10(11):1607-13
8592936
Osteoporos Int. 2005 Apr;16(4):411-6
15300362