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.


BACKGROUND
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.


METHODS
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.


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


METHODS
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.


CONCLUSIONS
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.
Mong
Janice L Y
JL
Department of Biochemistry, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, CHINA.
Ng
Maggie C Y
MC
Guldan
Georgia S
GS
Tam
Claudia H T
CH
Lee
Heung Man
HM
Ma
Ronald C W
RC
So
Wing Yee
WY
Wong
Gary W K
GW
Kong
Alice P S
AP
Chan
Juliana C N
JC
Waye
Mary M Y
MM
D050154:Adiposity; D000293:Adolescent; D000368:Aged; D000704:Analysis of Variance; D001823:Body Composition; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000097:blood / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011986:Receptors, Somatotropin / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D018972:Insulin-Like Growth Factor Binding Protein 3; D011986:Receptors, Somatotropin; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol