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.
Mong
J L Y
JL
Department of Biochemistry, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
Ng
M C Y
MC
Guldan
G S
GS
Tam
C H T
CH
Lee
H M
HM
Ma
R C W
RC
So
W Y
WY
Wong
G W K
GW
Kong
A P S
AP
Chan
J C N
JC
Waye
M M Y
MM
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