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A study of relationships between single nucleotide polymorphisms from the growth hormone-insulin-like growth factor axis and bone mass: the Hertfordshire cohort study

A study of relationships between single nucleotide polymorphisms from the growth hormone-insulin-like growth factor axis and bone mass: the Hertfordshire cohort study
A study of relationships between single nucleotide polymorphisms from the growth hormone-insulin-like growth factor axis and bone mass: the Hertfordshire cohort study
Objective: we sought evidence of association of candidate single nucleotide polymorphisms (SNP) within the growth hormone-insulin-like growth factor 1 (IGF1) axis, largely selected on the basis of functional data available at the time of our study, with adult bone mass.
Methods: four hundred ninety-eight men and 468 women aged 59–71 years were recruited. A lifestyle questionnaire was administered, and bone mineral content (BMC) and bone mineral density (BMD) were measured at the lumbar spine and femoral neck. Two hundred fifty-four men and 271 women had repeat bone densitometry 4 years later. DNA was obtained from whole blood samples using standard extraction techniques. Single nucleotide variants in the growth hormone releasing hormone gene (GHRH, G/A 223 Phe75Leu, rs4988492), growth hormone releasing hormone receptor gene (GHRHR, G/A 217, Ala57Thr, rs4988496), the growth hormone secretagogue receptor gene (GHSR, T/C, Gly57Gly, rs495225), and the growth hormone receptor gene (GHR, T/G, noncoding, rs2940944) were analyzed.
Results: in both sexes, allelic variation in the gene encoding GHRH was associated with BMC and BMD at the proximal femur and lumbar spine, with results generally stronger in women. In women, the mean BMC lumbar spine within the GHRH 11 genotype was 56.9 g, while that of the GHRH 12 genotype was 68.4 g [p < 0.001, fully adjusted for age, body mass index, cigarette and alcohol consumption, dietary calcium intake, physical activity, years since menopause, and hormone replacement therapy (HRT) use]; corresponding figures for BMD lumbar spine (GHRH 11 genotype) were 0.96 g/cm2 versus 1.10 g/cm2 (p < 0.001 fully adjusted).
Conclusion: we have demonstrated a relationship between allelic variation in the gene encoding GHRH and bone density; we welcome attempts at replication in other populations
0315-162X
1520-1526
Dennison, Elaine M.
ee647287-edb4-4392-8361-e59fd505b1d1
Syddall, Holly E.
a0181a93-8fc3-4998-a996-7963f0128328
Jameson, Karen A.
d5fb142d-06af-456e-9016-17497f94e9f2
Sayer, Avan Aihie
22ab6f4d-9d83-4272-9f56-1c2787598509
Gaunt, Tom R.
ff4bc39d-405c-4ba1-896b-7e7d2f747387
Rodriguez, Santiago
f235ea2b-b6f3-45e4-9fc3-5a0383689ed6
Day, Ian N.M.
b749b30a-1f4c-40eb-af0e-a50427388b39
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Lips, Mirjam A.
209cab24-aa31-47ca-b879-6e4a09c9f4b5
Dennison, Elaine M.
ee647287-edb4-4392-8361-e59fd505b1d1
Syddall, Holly E.
a0181a93-8fc3-4998-a996-7963f0128328
Jameson, Karen A.
d5fb142d-06af-456e-9016-17497f94e9f2
Sayer, Avan Aihie
22ab6f4d-9d83-4272-9f56-1c2787598509
Gaunt, Tom R.
ff4bc39d-405c-4ba1-896b-7e7d2f747387
Rodriguez, Santiago
f235ea2b-b6f3-45e4-9fc3-5a0383689ed6
Day, Ian N.M.
b749b30a-1f4c-40eb-af0e-a50427388b39
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Lips, Mirjam A.
209cab24-aa31-47ca-b879-6e4a09c9f4b5

Dennison, Elaine M., Syddall, Holly E., Jameson, Karen A., Sayer, Avan Aihie, Gaunt, Tom R., Rodriguez, Santiago, Day, Ian N.M., Cooper, Cyrus and Lips, Mirjam A. (2009) A study of relationships between single nucleotide polymorphisms from the growth hormone-insulin-like growth factor axis and bone mass: the Hertfordshire cohort study. Journal of Rheumatology, 36 (7), 1520-1526. (doi:10.3899/jrheum.081061).

Record type: Article

Abstract

Objective: we sought evidence of association of candidate single nucleotide polymorphisms (SNP) within the growth hormone-insulin-like growth factor 1 (IGF1) axis, largely selected on the basis of functional data available at the time of our study, with adult bone mass.
Methods: four hundred ninety-eight men and 468 women aged 59–71 years were recruited. A lifestyle questionnaire was administered, and bone mineral content (BMC) and bone mineral density (BMD) were measured at the lumbar spine and femoral neck. Two hundred fifty-four men and 271 women had repeat bone densitometry 4 years later. DNA was obtained from whole blood samples using standard extraction techniques. Single nucleotide variants in the growth hormone releasing hormone gene (GHRH, G/A 223 Phe75Leu, rs4988492), growth hormone releasing hormone receptor gene (GHRHR, G/A 217, Ala57Thr, rs4988496), the growth hormone secretagogue receptor gene (GHSR, T/C, Gly57Gly, rs495225), and the growth hormone receptor gene (GHR, T/G, noncoding, rs2940944) were analyzed.
Results: in both sexes, allelic variation in the gene encoding GHRH was associated with BMC and BMD at the proximal femur and lumbar spine, with results generally stronger in women. In women, the mean BMC lumbar spine within the GHRH 11 genotype was 56.9 g, while that of the GHRH 12 genotype was 68.4 g [p < 0.001, fully adjusted for age, body mass index, cigarette and alcohol consumption, dietary calcium intake, physical activity, years since menopause, and hormone replacement therapy (HRT) use]; corresponding figures for BMD lumbar spine (GHRH 11 genotype) were 0.96 g/cm2 versus 1.10 g/cm2 (p < 0.001 fully adjusted).
Conclusion: we have demonstrated a relationship between allelic variation in the gene encoding GHRH and bone density; we welcome attempts at replication in other populations

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Published date: July 2009
Organisations: Dev Origins of Health & Disease

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Local EPrints ID: 69398
URI: http://eprints.soton.ac.uk/id/eprint/69398
ISSN: 0315-162X
PURE UUID: b89ddfa4-3882-4dd2-b1bd-fde1deeedbce
ORCID for Elaine M. Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for Holly E. Syddall: ORCID iD orcid.org/0000-0003-0171-0306
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 09 Nov 2009
Last modified: 18 Mar 2024 02:48

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Contributors

Author: Avan Aihie Sayer
Author: Tom R. Gaunt
Author: Santiago Rodriguez
Author: Ian N.M. Day
Author: Cyrus Cooper ORCID iD
Author: Mirjam A. Lips

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