Polymorphism in the Growth Hormone Gene, Weight in Infancy, and Adult Bone Mass
E. M. Dennison,
H. E. Syddall,
S. Rodriguez,
A. Voropanov,
I. N. M. Day and
C. Cooper the Southampton Genetic Epidemiology Research Group
Medical Research Council Epidemiology Resource Center (E.M.D., H.E.S., C.C.) and Human Genetics Division (S.R., A.V., I.N.M.D.), University of Southampton, Southampton General Hospital, Southampton, United Kingdom SO16 6YD
Address all correspondence and requests for reprints to: Dr. Elaine Dennison, Medical Research Council Resource Center, Southampton General Hospital, Southampton, United Kingdom SO16 6YD. E-mail: emd{at}mrc.soton.ac.uk.
Epidemiological studies point to the importance of gene-environmentinteractions during early life as determinants of later osteoporosisand fracture. We examined associations between common singlenucleotide polymorphisms in the human GH (GH1) gene and weightin infancy, adult bone mass and bone loss rates, and circulatingGH profiles. Two hundred and five men and 132 women, aged 61–73yr, in the Hertfordshire Cohort Study were included; bone mineraldensity was measured by dual energy x-ray absorptiometry over4 yr. Twenty-four-hour circulating GH profiles were constructedin a subset of 71 men and women. Genomic DNA was examined fortwo single nucleotide polymorphisms in the GH gene (one in thepromoter region and one in intron 4). Homozygotes at loci GH1A5157G and T6331A displayed low baseline bone density and acceleratedbone loss; there was also a significant (P = 0.04) interactionamong weight at 1 yr, GH1 genotype, and bone loss rate. Therewas a graded association between alleles and circulating GHconcentration among men. This study suggests that common diversityin the GH1 region predisposes to osteoporosis via effects onthe level of GH expression. The interaction with infant weightsuggests that early environment may influence the effect ofGH1 genotype on bone loss.
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