Associations of insulin-like growth factor binding protein-3 gene polymorphisms with IGF-I activity and lipid parameters in adolescents.
OBJECTIVE
Childhood obesity is a growing global epidemic. Recent studies indicate that obesity and related metabolic traits are highly heritable. Increasing evidence suggests that growth hormone (GH) and the insulin-like growth factor-I (IGF-I) axis have important functions in regulating adiposity and insulin sensitivity. Five single-nucleotide polymorphisms (SNPs) at IGF-binding protein-3 (IGFBP3) were genotyped to find their associations with IGF-1 activity level and common clinical metabolic traits.


METHODS
We examined the associations of five SNPs at IGFBP3 with serum IGF-I and IGFBP-3 levels, as well as with obesity-related metabolic traits in 981 Hong Kong Chinese adolescents. Factor analysis was used to reduce the intercorrelated variables to five factor scores indicating body composition, blood pressure, IGF-I activity, triglyceride (TG)+high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC)+low-density lipoprotein cholesterol (LDL-C) factor scores.


RESULTS
There was a strong association between the -202A/C polymorphism (rs2854744) and IGF-I activity (P=1.2 x 10(-6)) and TC+LDL-C factor scores (P=0.0085), corrected for age and sex. The C allele was associated with decreased IGFBP-3 levels (P=1.21 x 10(-13)), increased IGF-I/IGFBP-3 molar ratio (P=5.22 x 10(-6)) and decreased LDL-C (P=0.020). There was also a significant association between a G/A polymorphism at the 3' flanking sequence (rs13223993) of the IGFBP3 gene and the TG+HDL-C factor score (P=0.0013). The minor A allele carriers of rs13223993 had a lower HDL-C (P=0.0067) level and a tendency toward a high TG level. Haplotype analysis did not increase the significance of associations between single SNPs and phenotypes.


CONCLUSIONS
Our results support the function of IGFBP3 gene polymorphisms in modulating IGF-I activity and lipid levels in adolescents. Given the prognostic significance of IGF-I, IGFBPs and lipids on risk of diabetes, obesity and cancer, long-term studies are required to clarify the clinical meaning of these findings.
Department of Biochemistry, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
J L Y
JL
Mong
M C Y
MC
Ng
G S
GS
Guldan
C H T
CH
Tam
H M
HM
Lee
R C W
RC
Ma
W Y
WY
So
G W K
GW
Wong
A P S
AP
Kong
J C N
JC
Chan
M M Y
MM
Waye
D000293:Adolescent; D001823:Body Composition / Q000235:genetics; D005260:Female; D005838:Genotype; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008055:Lipids / Q000097:blood* / Q000235:genetics; D008297:Male; D009765:Obesity / Q000097:blood* / Q000453:epidemiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D018972:Insulin-Like Growth Factor Binding Protein 3; D008055:Lipids; D007334:Insulin-Like Growth Factor I