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Polymorphism in the growth hormone gene, weight in infancy, and adult bone mass

Polymorphism in the growth hormone gene, weight in infancy, and adult bone mass
Polymorphism in the growth hormone gene, weight in infancy, and adult bone mass
Epidemiological studies point to the importance of gene-environment interactions during early life as determinants of later osteoporosis and fracture. We examined associations between common single nucleotide polymorphisms in the human GH (GH1) gene and weight in infancy, adult bone mass and bone loss rates, and circulating GH profiles. Two hundred and five men and 132 women, aged 61–73 yr, in the Hertfordshire Cohort Study were included; bone mineral density was measured by dual energy x-ray absorptiometry over 4 yr. Twenty-four-hour circulating GH profiles were constructed in a subset of 71 men and women. Genomic DNA was examined for two single nucleotide polymorphisms in the GH gene (one in the promoter region and one in intron 4). Homozygotes at loci GH1 A5157G and T6331A displayed low baseline bone density and accelerated bone loss; there was also a significant (P = 0.04) interaction among weight at 1 yr, GH1 genotype, and bone loss rate. There was a graded association between alleles and circulating GH concentration among men. This study suggests that common diversity in the GH1 region predisposes to osteoporosis via effects on the level of GH expression. The interaction with infant weight suggests that early environment may influence the effect of GH1 genotype on bone loss.
0021-972X
4898-4903
Dennison, E.M.
ee647287-edb4-4392-8361-e59fd505b1d1
Syddall, H.E.
a0181a93-8fc3-4998-a996-7963f0128328
Rodriguez, S.
b047a823-28c8-4043-8d4f-dc6b23f52e4e
Voropanov, A.
8e58918a-de97-45a4-9d61-2f23f9177ecd
Day, I.N.M.
1a55713e-ee42-4f9c-9867-955202528f17
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Tabassum, Faiza
a4bcd2d6-c576-4e85-8ba4-c3b4bb1ade08
The Southampton Genetic Epidemiology Research Group
Dennison, E.M.
ee647287-edb4-4392-8361-e59fd505b1d1
Syddall, H.E.
a0181a93-8fc3-4998-a996-7963f0128328
Rodriguez, S.
b047a823-28c8-4043-8d4f-dc6b23f52e4e
Voropanov, A.
8e58918a-de97-45a4-9d61-2f23f9177ecd
Day, I.N.M.
1a55713e-ee42-4f9c-9867-955202528f17
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Tabassum, Faiza
a4bcd2d6-c576-4e85-8ba4-c3b4bb1ade08

Dennison, E.M., Syddall, H.E., Rodriguez, S., Voropanov, A., Day, I.N.M., Cooper, C. and Tabassum, Faiza , The Southampton Genetic Epidemiology Research Group (2004) Polymorphism in the growth hormone gene, weight in infancy, and adult bone mass. Journal of Clinical Endocrinology and Metabolism, 89 (10), 4898-4903. (doi:10.1210/jc.2004-0151).

Record type: Article

Abstract

Epidemiological studies point to the importance of gene-environment interactions during early life as determinants of later osteoporosis and fracture. We examined associations between common single nucleotide polymorphisms in the human GH (GH1) gene and weight in infancy, adult bone mass and bone loss rates, and circulating GH profiles. Two hundred and five men and 132 women, aged 61–73 yr, in the Hertfordshire Cohort Study were included; bone mineral density was measured by dual energy x-ray absorptiometry over 4 yr. Twenty-four-hour circulating GH profiles were constructed in a subset of 71 men and women. Genomic DNA was examined for two single nucleotide polymorphisms in the GH gene (one in the promoter region and one in intron 4). Homozygotes at loci GH1 A5157G and T6331A displayed low baseline bone density and accelerated bone loss; there was also a significant (P = 0.04) interaction among weight at 1 yr, GH1 genotype, and bone loss rate. There was a graded association between alleles and circulating GH concentration among men. This study suggests that common diversity in the GH1 region predisposes to osteoporosis via effects on the level of GH expression. The interaction with infant weight suggests that early environment may influence the effect of GH1 genotype on bone loss.

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More information

Published date: October 2004

Identifiers

Local EPrints ID: 24684
URI: https://eprints.soton.ac.uk/id/eprint/24684
ISSN: 0021-972X
PURE UUID: f59e6b3a-1562-4bf3-91ef-5429a1e69b6d
ORCID for E.M. Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for H.E. Syddall: ORCID iD orcid.org/0000-0003-0171-0306
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 03 Apr 2006
Last modified: 10 Jan 2019 01:37

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