Klotho Gene Polymorphisms are Associated with Osteocalcin Levels but not Bone Denisty of Aged Postmenopausal Women

B.H. Mullin, S.G. Wilson, F.M.A. Islam, M. Calautti, Ian Dick, A. Devine, Richard Prince

Research output: Contribution to journalArticle

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Abstract

Osteoporosis is known to have a strong genetic basis. It has been proposed that polymorphisms within the KL (klotho) gene have a significant effect on aging, in particular, the osteoblast defect of aging. The association between polymorphisms within this gene and biochemical markers of bone formation and resorption, bone structure, and fracture rates was studied in 1,190 postmenopausal women with a mean age of 75 years. Genotyping of these polymorphic sites was carried out using Matrix-Assisted Laser Desorption Ionization-Time of Flight (MALDI-ToF) mass spectrometry. The G allele of SNP c. 1775G > A was associated with a lower osteocalcin level than the A allele (P = 0.004) in a codominant model. SNPs C-387T and IVS1+8262c > t both showed nonsignificant associations with osteocalcin (P values of 0.063 and 0.068, respectively), but a haplotype analysis of 2 of 5 haplotypes of the three SNPs with a frequency greater than 4% revealed a significant association with osteocalcin (P = 0.036). None of the individual polymorphisms or haplotypes analyzed showed any associations with a marker of bone resorption the deoxypyridinoline creatinine ratio, bone structure, or fracture data. Therefore, the G polymorphism within the c.1775G > A SNP sit, and a haplotype including this are, associated with a reduced osteoblast product osteocalcin. These data suggest that variation in the KL gene product affects osteoblast activity independent of osteoclast activity but that this defect does not result in an effect on bone structure in this population, perhaps because of "rescue" by other genetic or environmental factors in this population.
Original languageEnglish
Pages (from-to)145-151
JournalCalcified Tissue International
Volume77
Issue number3
DOIs
Publication statusPublished - 2005

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Osteocalcin
Haplotypes
Single Nucleotide Polymorphism
Osteoblasts
Bone and Bones
Bone Resorption
Genes
Alleles
Bone Fractures
Osteoclasts
Osteogenesis
Population
Osteoporosis
Mass Spectrometry
Creatinine
Lasers
Biomarkers

Cite this

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title = "Klotho Gene Polymorphisms are Associated with Osteocalcin Levels but not Bone Denisty of Aged Postmenopausal Women",
abstract = "Osteoporosis is known to have a strong genetic basis. It has been proposed that polymorphisms within the KL (klotho) gene have a significant effect on aging, in particular, the osteoblast defect of aging. The association between polymorphisms within this gene and biochemical markers of bone formation and resorption, bone structure, and fracture rates was studied in 1,190 postmenopausal women with a mean age of 75 years. Genotyping of these polymorphic sites was carried out using Matrix-Assisted Laser Desorption Ionization-Time of Flight (MALDI-ToF) mass spectrometry. The G allele of SNP c. 1775G > A was associated with a lower osteocalcin level than the A allele (P = 0.004) in a codominant model. SNPs C-387T and IVS1+8262c > t both showed nonsignificant associations with osteocalcin (P values of 0.063 and 0.068, respectively), but a haplotype analysis of 2 of 5 haplotypes of the three SNPs with a frequency greater than 4{\%} revealed a significant association with osteocalcin (P = 0.036). None of the individual polymorphisms or haplotypes analyzed showed any associations with a marker of bone resorption the deoxypyridinoline creatinine ratio, bone structure, or fracture data. Therefore, the G polymorphism within the c.1775G > A SNP sit, and a haplotype including this are, associated with a reduced osteoblast product osteocalcin. These data suggest that variation in the KL gene product affects osteoblast activity independent of osteoclast activity but that this defect does not result in an effect on bone structure in this population, perhaps because of {"}rescue{"} by other genetic or environmental factors in this population.",
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Klotho Gene Polymorphisms are Associated with Osteocalcin Levels but not Bone Denisty of Aged Postmenopausal Women. / Mullin, B.H.; Wilson, S.G.; Islam, F.M.A.; Calautti, M.; Dick, Ian; Devine, A.; Prince, Richard.

In: Calcified Tissue International, Vol. 77, No. 3, 2005, p. 145-151.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Klotho Gene Polymorphisms are Associated with Osteocalcin Levels but not Bone Denisty of Aged Postmenopausal Women

AU - Mullin, B.H.

AU - Wilson, S.G.

AU - Islam, F.M.A.

AU - Calautti, M.

AU - Dick, Ian

AU - Devine, A.

AU - Prince, Richard

PY - 2005

Y1 - 2005

N2 - Osteoporosis is known to have a strong genetic basis. It has been proposed that polymorphisms within the KL (klotho) gene have a significant effect on aging, in particular, the osteoblast defect of aging. The association between polymorphisms within this gene and biochemical markers of bone formation and resorption, bone structure, and fracture rates was studied in 1,190 postmenopausal women with a mean age of 75 years. Genotyping of these polymorphic sites was carried out using Matrix-Assisted Laser Desorption Ionization-Time of Flight (MALDI-ToF) mass spectrometry. The G allele of SNP c. 1775G > A was associated with a lower osteocalcin level than the A allele (P = 0.004) in a codominant model. SNPs C-387T and IVS1+8262c > t both showed nonsignificant associations with osteocalcin (P values of 0.063 and 0.068, respectively), but a haplotype analysis of 2 of 5 haplotypes of the three SNPs with a frequency greater than 4% revealed a significant association with osteocalcin (P = 0.036). None of the individual polymorphisms or haplotypes analyzed showed any associations with a marker of bone resorption the deoxypyridinoline creatinine ratio, bone structure, or fracture data. Therefore, the G polymorphism within the c.1775G > A SNP sit, and a haplotype including this are, associated with a reduced osteoblast product osteocalcin. These data suggest that variation in the KL gene product affects osteoblast activity independent of osteoclast activity but that this defect does not result in an effect on bone structure in this population, perhaps because of "rescue" by other genetic or environmental factors in this population.

AB - Osteoporosis is known to have a strong genetic basis. It has been proposed that polymorphisms within the KL (klotho) gene have a significant effect on aging, in particular, the osteoblast defect of aging. The association between polymorphisms within this gene and biochemical markers of bone formation and resorption, bone structure, and fracture rates was studied in 1,190 postmenopausal women with a mean age of 75 years. Genotyping of these polymorphic sites was carried out using Matrix-Assisted Laser Desorption Ionization-Time of Flight (MALDI-ToF) mass spectrometry. The G allele of SNP c. 1775G > A was associated with a lower osteocalcin level than the A allele (P = 0.004) in a codominant model. SNPs C-387T and IVS1+8262c > t both showed nonsignificant associations with osteocalcin (P values of 0.063 and 0.068, respectively), but a haplotype analysis of 2 of 5 haplotypes of the three SNPs with a frequency greater than 4% revealed a significant association with osteocalcin (P = 0.036). None of the individual polymorphisms or haplotypes analyzed showed any associations with a marker of bone resorption the deoxypyridinoline creatinine ratio, bone structure, or fracture data. Therefore, the G polymorphism within the c.1775G > A SNP sit, and a haplotype including this are, associated with a reduced osteoblast product osteocalcin. These data suggest that variation in the KL gene product affects osteoblast activity independent of osteoclast activity but that this defect does not result in an effect on bone structure in this population, perhaps because of "rescue" by other genetic or environmental factors in this population.

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M3 - Article

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SP - 145

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JO - Calcified Tissue International

JF - Calcified Tissue International

SN - 0171-967X

IS - 3

ER -