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/cm(2) versus 1.10 g/cm(2) (p < 0.001 fully adjusted).


CONCLUSIONS
We have demonstrated a relationship between allelic variation in the gene encoding GHRH and bone density; we welcome attempts at replication in other populations.
Dennison
Elaine M
EM
MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, England, UK. emd@mrc.soton.ac.uk
Syddall
Holly E
HE
Jameson
Karen A
KA
Sayer
Avan Aihie
AA
Gaunt
Tom R
TR
Rodriguez
Santiago
S
Day
Ian N M
IN
Cooper
Cyrus
C
Lips
Mirjam A
MA
D000368:Aged; D015519:Bone Density / Q000235:genetics* / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D013006:Growth Hormone / Q000235:genetics* / Q000502:physiology*; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics; D006306:Health Surveys; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054440:Receptors, Ghrelin / Q000235:genetics; D018013:Receptors, Neuropeptide / Q000235:genetics; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics; D012307:Risk Factors; D006113:United Kingdom
D054440:Receptors, Ghrelin; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor