A study of association between common variation in the growth hormone-chorionic somatomammotropin hormone gene cluster and adult fasting insulin in a UK Caucasian population.
BACKGROUND
Reduced growth during infancy is associated with adult insulin resistance. In a UK Caucasian cohort, the CSH1.01 microsatellite polymorphism in the growth hormone-chorionic somatomammotropin hormone gene cluster was recently associated with increases in adult fasting insulin of approximately 23 pmol/l for TT homozygote males compared to D1D1 or D2D2 homozygotes (P = 0.001 and 0.009; n = 206 and 92, respectively), but not for females. TT males additionally had a 547-g lower weight at 1 year (n = 270; P = 0.008) than D2D2 males. We sought to replicate these data in healthy UK Caucasian subjects. We genotyped 1396 subjects (fathers, mothers and children) from a consecutive birth study for the CSH1.01 marker and analysed genotypes for association with 1-year weight in boys and fasting insulin in fathers.


RESULTS
We found no evidence for association of CSH1.01 genotype with adult male fasting insulin concentrations (TT/D1D1 P = 0.38; TT/D2D2 P = 0.18) or weight at 1 year in boys (TT/D1D1 P = 0.76; TT/D2D2 P = 0.85). For fasting insulin, our data can exclude the previously observed effect sizes as the 95 % confidence intervals for the differences observed in our study exclude increases in fasting insulin of 9.0 and 12.6 pmol/l for TT relative to D1D1 and D2D2 homozygotes, respectively. Whilst we have fewer data on boys' 1-year weight than the original study, our data can exclude a reduction in 1-year weight greater than 557 g for TT relative to D2D2 homozygotes.


CONCLUSIONS
We have not found association of the CSH1.01 genotype with fasting insulin or weight at 1 year. We conclude that the original study is likely to have over-estimated the effect size for fasting insulin, or that the difference in results reflects the younger age of subjects in this study relative to those in the previous study.
Freathy
Rachel M
RM
Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK. rachel.freathy@pms.ac.uk
Mitchell
Simon M S
SM
Knight
Beatrice
B
Shields
Beverley
B
Weedon
Michael N
MN
Hattersley
Andrew T
AT
Frayling
Timothy M
TM
D000328:Adult; D001835:Body Weight; D015331:Cohort Studies; D005215:Fasting / Q000097:blood*; D005220:Fathers; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D007223:Infant; D007328:Insulin / Q000097:blood*; D008297:Male; D018895:Microsatellite Repeats; D005810:Multigene Family; D009994:Osmolar Concentration; D010641:Phenotype; D010928:Placental Lactogen / Q000235:genetics*; D011110:Polymorphism, Genetic; D006113:United Kingdom; D044465:White People
D007328:Insulin; D013006:Growth Hormone; D010928:Placental Lactogen