title: 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.
abstract: 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.
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK. rachel.freathy@pms.ac.uk
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Freathy
authors.forename: Simon M S
authors.initials: SM
authors.lastname: Mitchell
authors.forename: Beatrice
authors.initials: B
authors.lastname: Knight
authors.forename: Beverley
authors.initials: B
authors.lastname: Shields
authors.forename: Michael N
authors.initials: MN
authors.lastname: Weedon
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
mesh_terms: 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
chemical_list: D007328:Insulin; D013006:Growth Hormone; D010928:Placental Lactogen