| Associations of insulin-like growth factor binding protein-3 gene polymorphisms with IGF-I activity and lipid parameters in adolescents. | |
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MedLine Citation:
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PMID: 19786971 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. PATIENTS AND 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. CONCLUSION: 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. |
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Authors:
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J L Y Mong; M C Y Ng; G S Guldan; C H T Tam; H M Lee; R C W Ma; W Y So; G W K Wong; A P S Kong; J C N Chan; M M Y Waye |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of obesity (2005) Volume: 33 ISSN: 1476-5497 ISO Abbreviation: Int J Obes (Lond) Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-16 Completed Date: 2010-10-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101256108 Medline TA: Int J Obes (Lond) Country: England |
Other Details:
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Languages: eng Pagination: 1446-53 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Body Composition / genetics Female Genotype Hong Kong / epidemiology Humans Insulin-Like Growth Factor Binding Protein 3 / blood, genetics* Insulin-Like Growth Factor I / metabolism* Lipids / blood*, genetics Male Obesity / blood*, epidemiology Phenotype Polymorphism, Single Nucleotide / genetics |
| Chemical | |
Reg. No./Substance:
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0/Insulin-Like Growth Factor Binding Protein 3; 0/Lipids; 67763-96-6/Insulin-Like Growth Factor I |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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