LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women

J. Bollerslev, S.G. Wilson, Ian Dick, F.M.A. Islam, T. Ueland, Lyle Palmer, A. Devine, Richard Prince

Research output: Contribution to journalArticle

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Abstract

Postmenopausal osteoporosis and bone mass are influenced by multiple factors including genetic variation. The importance of LDL receptor-related protein 5 (LRP5) for the regulation of bone mass has recently been established, where loss of function mutations is followed by severe osteoporosis and gain of function is related to increased bone mass. The aim of this study was to evaluate the role of polymorphisms in the LRP5 gene in regulating bone mass and influencing prospective fracture frequency in a well-described, large cohort of normal, ambulatory Australian women. A total of 1301 women were genotyped for seven different single nucleotide polymorphisms (SNPs) within the LRP5 gene of which five were potentially informative. The effects of these gene polymorphisms on calcaneal quantitative ultrasound measurements (QUS), osteodensitometry of the hip and bone-related biochemistry was examined. One SNP located in exert 15 was found to be associated with fracture rate and bone mineral density. Homozygosity for the less frequent allele of c.3357A > G was associated with significant reduction in bone mass at most femoral sites. The subjects with the GG genotype, compared to the AA/AG genotypes showed a significant reduction in BUA and total hip, femoral neck and trochanter BMD (1.5% P = 0.032; 2.7% P = 0.047; 3.6% P = 0.008; 3.1% P = 0.050, respectively). In the 5-year follow-tip period, 227 subjects experienced a total of 290 radiologically confirmed fractures. The incident fracture rate was significantly increased in subjects homozygous for the GG polymorphism (RR of fracture = 1.61, 95% CI [1.06-2.45], P = 0.027). After adjusting for total hip BMD, the fracture rate was still increased (RR = 1.67 [1.02-2.78], P = 0.045), indicating factors other than bone mass are of importance for bone strength. In conclusion, genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures. © 2005 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)599-606
JournalBone
Volume36
Issue number4
DOIs
Publication statusPublished - 2005

Fingerprint

Low Density Lipoprotein Receptor-Related Protein-1
Bone and Bones
Genes
Single Nucleotide Polymorphism
Genotype
Pelvic Bones
Postmenopausal Osteoporosis
Osteoporotic Fractures
Femur Neck
Bone Fractures
Hip Fractures
Thigh
Biochemistry
Bone Density
Femur
Osteoporosis
Hip
Alleles
Mutation

Cite this

Bollerslev, J. ; Wilson, S.G. ; Dick, Ian ; Islam, F.M.A. ; Ueland, T. ; Palmer, Lyle ; Devine, A. ; Prince, Richard. / LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women. In: Bone. 2005 ; Vol. 36, No. 4. pp. 599-606.
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abstract = "Postmenopausal osteoporosis and bone mass are influenced by multiple factors including genetic variation. The importance of LDL receptor-related protein 5 (LRP5) for the regulation of bone mass has recently been established, where loss of function mutations is followed by severe osteoporosis and gain of function is related to increased bone mass. The aim of this study was to evaluate the role of polymorphisms in the LRP5 gene in regulating bone mass and influencing prospective fracture frequency in a well-described, large cohort of normal, ambulatory Australian women. A total of 1301 women were genotyped for seven different single nucleotide polymorphisms (SNPs) within the LRP5 gene of which five were potentially informative. The effects of these gene polymorphisms on calcaneal quantitative ultrasound measurements (QUS), osteodensitometry of the hip and bone-related biochemistry was examined. One SNP located in exert 15 was found to be associated with fracture rate and bone mineral density. Homozygosity for the less frequent allele of c.3357A > G was associated with significant reduction in bone mass at most femoral sites. The subjects with the GG genotype, compared to the AA/AG genotypes showed a significant reduction in BUA and total hip, femoral neck and trochanter BMD (1.5{\%} P = 0.032; 2.7{\%} P = 0.047; 3.6{\%} P = 0.008; 3.1{\%} P = 0.050, respectively). In the 5-year follow-tip period, 227 subjects experienced a total of 290 radiologically confirmed fractures. The incident fracture rate was significantly increased in subjects homozygous for the GG polymorphism (RR of fracture = 1.61, 95{\%} CI [1.06-2.45], P = 0.027). After adjusting for total hip BMD, the fracture rate was still increased (RR = 1.67 [1.02-2.78], P = 0.045), indicating factors other than bone mass are of importance for bone strength. In conclusion, genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures. © 2005 Elsevier Inc. All rights reserved.",
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LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women. / Bollerslev, J.; Wilson, S.G.; Dick, Ian; Islam, F.M.A.; Ueland, T.; Palmer, Lyle; Devine, A.; Prince, Richard.

In: Bone, Vol. 36, No. 4, 2005, p. 599-606.

Research output: Contribution to journalArticle

TY - JOUR

T1 - LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women

AU - Bollerslev, J.

AU - Wilson, S.G.

AU - Dick, Ian

AU - Islam, F.M.A.

AU - Ueland, T.

AU - Palmer, Lyle

AU - Devine, A.

AU - Prince, Richard

PY - 2005

Y1 - 2005

N2 - Postmenopausal osteoporosis and bone mass are influenced by multiple factors including genetic variation. The importance of LDL receptor-related protein 5 (LRP5) for the regulation of bone mass has recently been established, where loss of function mutations is followed by severe osteoporosis and gain of function is related to increased bone mass. The aim of this study was to evaluate the role of polymorphisms in the LRP5 gene in regulating bone mass and influencing prospective fracture frequency in a well-described, large cohort of normal, ambulatory Australian women. A total of 1301 women were genotyped for seven different single nucleotide polymorphisms (SNPs) within the LRP5 gene of which five were potentially informative. The effects of these gene polymorphisms on calcaneal quantitative ultrasound measurements (QUS), osteodensitometry of the hip and bone-related biochemistry was examined. One SNP located in exert 15 was found to be associated with fracture rate and bone mineral density. Homozygosity for the less frequent allele of c.3357A > G was associated with significant reduction in bone mass at most femoral sites. The subjects with the GG genotype, compared to the AA/AG genotypes showed a significant reduction in BUA and total hip, femoral neck and trochanter BMD (1.5% P = 0.032; 2.7% P = 0.047; 3.6% P = 0.008; 3.1% P = 0.050, respectively). In the 5-year follow-tip period, 227 subjects experienced a total of 290 radiologically confirmed fractures. The incident fracture rate was significantly increased in subjects homozygous for the GG polymorphism (RR of fracture = 1.61, 95% CI [1.06-2.45], P = 0.027). After adjusting for total hip BMD, the fracture rate was still increased (RR = 1.67 [1.02-2.78], P = 0.045), indicating factors other than bone mass are of importance for bone strength. In conclusion, genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures. © 2005 Elsevier Inc. All rights reserved.

AB - Postmenopausal osteoporosis and bone mass are influenced by multiple factors including genetic variation. The importance of LDL receptor-related protein 5 (LRP5) for the regulation of bone mass has recently been established, where loss of function mutations is followed by severe osteoporosis and gain of function is related to increased bone mass. The aim of this study was to evaluate the role of polymorphisms in the LRP5 gene in regulating bone mass and influencing prospective fracture frequency in a well-described, large cohort of normal, ambulatory Australian women. A total of 1301 women were genotyped for seven different single nucleotide polymorphisms (SNPs) within the LRP5 gene of which five were potentially informative. The effects of these gene polymorphisms on calcaneal quantitative ultrasound measurements (QUS), osteodensitometry of the hip and bone-related biochemistry was examined. One SNP located in exert 15 was found to be associated with fracture rate and bone mineral density. Homozygosity for the less frequent allele of c.3357A > G was associated with significant reduction in bone mass at most femoral sites. The subjects with the GG genotype, compared to the AA/AG genotypes showed a significant reduction in BUA and total hip, femoral neck and trochanter BMD (1.5% P = 0.032; 2.7% P = 0.047; 3.6% P = 0.008; 3.1% P = 0.050, respectively). In the 5-year follow-tip period, 227 subjects experienced a total of 290 radiologically confirmed fractures. The incident fracture rate was significantly increased in subjects homozygous for the GG polymorphism (RR of fracture = 1.61, 95% CI [1.06-2.45], P = 0.027). After adjusting for total hip BMD, the fracture rate was still increased (RR = 1.67 [1.02-2.78], P = 0.045), indicating factors other than bone mass are of importance for bone strength. In conclusion, genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures. © 2005 Elsevier Inc. All rights reserved.

U2 - 10.1016/j.bone.2005.01.006

DO - 10.1016/j.bone.2005.01.006

M3 - Article

VL - 36

SP - 599

EP - 606

JO - Bone

JF - Bone

SN - 8756-3282

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ER -