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Prospective study of insulin-like growth factor-I, insulin-like growth factor-binding protein 3, genetic variants in the IGF1 and IGFBP3 genes and risk of coronary artery disease.


ABSTRACT: Although experimental studies have suggested that insulin-like growth factor I (IGF-I) and its binding protein IGFBP-3 might have a role in the aetiology of coronary artery disease (CAD), the relevance of circulating IGFs and their binding proteins in the development of CAD in human populations is unclear. We conducted a nested case-control study, with a mean follow-up of six years, within the EPIC-Norfolk cohort to assess the association between circulating levels of IGF-I and IGFBP-3 and risk of CAD in up to 1,013 cases and 2,055 controls matched for age, sex and study enrolment date. After adjustment for cardiovascular risk factors, we found no association between circulating levels of IGF-I or IGFBP-3 and risk of CAD (odds ratio: 0.98 (95% Cl 0.90-1.06) per 1 SD increase in circulating IGF-I; odds ratio: 1.02 (95% Cl 0.94-1.12) for IGFBP-3). We examined associations between tagging single nucleotide polymorphisms (tSNPs) at the IGF1 and IGFBP3 loci and circulating IGF-I and IGFBP-3 levels in up to 1,133 cases and 2,223 controls and identified three tSNPs (rs1520220, rs3730204, rs2132571) that showed independent association with either circulating IGF-I or IGFBP-3 levels. In an assessment of 31 SNPs spanning the IGF1 or IGFBP3 loci, none were associated with risk of CAD in a meta-analysis that included EPIC-Norfolk and eight additional studies comprising up to 9,319 cases and 19,964 controls. Our results indicate that IGF-I and IGFBP-3 are unlikely to be importantly involved in the aetiology of CAD in human populations.

SUBMITTER: Ricketts SL 

PROVIDER: S-EPMC3166154 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Prospective study of insulin-like growth factor-I, insulin-like growth factor-binding protein 3, genetic variants in the IGF1 and IGFBP3 genes and risk of coronary artery disease.

Ricketts Sally L SL   Rensing Katrijn L KL   Holly Jeff M JM   Chen Li L   Young Elizabeth H EH   Luben Robert R   Ashford Sofie S   Song Kijoung K   Yuan Xin X   Dehghan Abbas A   Wright Benjamin J BJ   Waterworth Dawn M DM   Mooser Vincent V   Waeber Gérard G   Vollenweider Peter P   Epstein Stephen E SE   Burnett Mary S MS   Devaney Joseph M JM   Hakonarson Hakon H HH   Rader Daniel J DJ   Reilly Muredach P MP   Danesh John J   Thompson Simon G SG   Dunning Alison M AM   van Duijn Cornelia M CM   Samani Nilesh J NJ   McPherson Ruth R   Wareham Nicholas J NJ   Khaw Kay-Tee KT   Boekholdt S Matthijs SM   Sandhu Manjinder S MS  

International journal of molecular epidemiology and genetics 20110803 3


Although experimental studies have suggested that insulin-like growth factor I (IGF-I) and its binding protein IGFBP-3 might have a role in the aetiology of coronary artery disease (CAD), the relevance of circulating IGFs and their binding proteins in the development of CAD in human populations is unclear. We conducted a nested case-control study, with a mean follow-up of six years, within the EPIC-Norfolk cohort to assess the association between circulating levels of IGF-I and IGFBP-3 and risk  ...[more]

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