Associations of the growth hormone receptor (GHR) gene polymorphisms with adiposity and IGF-I activity in adolescents.

OBJECTIVE

To explore the genetic effect of the GH receptor (GHR) on obesity and related metabolic parameters in Hong Kong Chinese adolescents.

CONTEXT

Obesity is a growing global epidemic. Increasing evidence suggests that the GH-IGF-I axis plays an important role in regulating adiposity and insulin sensitivity.

DESIGN

We examined the associations of genetic variants of GHR with serum IGF-I and IGFBP-3 levels as well as obesity-related metabolic traits in Hong Kong Chinese adolescents.

PATIENTS

Nine hundred and eighty-one randomly selected Hong Kong Chinese adolescents from 14 schools.

MEASUREMENTS

We genotyped 17 single nucleotide polymorphisms (SNP) at GHR and measured serum IGF-I and IGFBP-3 levels as well as obesity-related metabolic traits including fasting plasma glucose, insulin and lipid levels.

RESULTS

There were significant associations between rs4410646 and the body composition (P = 0.0044) and blood pressure factor scores (P = 0.00017). Carriers of the CC genotype had lower body mass index, percentage body fat, waist and hip circumferences than AC and AA genotype carriers (P = 0.00030-0.0094). There was also association between rs7703713 and the IGF-I activity factor score (P = 0.0033). The GA and AA carriers of rs7703713 had higher serum IGF-I, higher serum IGFBP-3 and higher IGF-I/IGFBP-3 molar ratio (P = 0.00069-0.025). Haplotype analysis did not increase the significance of associations.

CONCLUSION

Our results support the role of GHR gene polymorphisms in modulating adiposity and IGF-I activity in adolescents. Examination of interactions of these SNPs with lifestyle, environmental and perinatal factors may provide further insights into their long-term effects on obesity and metabolic risks.